bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered CD45 isoform expression in C77G carriers influences cytokine responsiveness and adhesion properties of T cells
Authors: Windhagen A , Sönmez D , Hornig-Do H T , Kalinowsky A , Schwinzer R
Published: July 2010

The C77G polymorphism in exon A of the human CD45 gene occurs with low frequency in healthy individuals. An enhanced frequency of C77G individuals has been reported in cohorts of patients suffering from multiple sclerosis, systemic sclerosis, autoimmune hepatitis, hepatitis C and human immunodeficiency virus (HIV)-1. C77G individuals overexpress CD45RA isoforms on activated/memory T cells. We have shown previously that aberrant expression of CD45RA isoforms enhances the intensity of T cell receptor (TCR) signalling. Here we report that the C77G polymorphism also influences the responsiveness of T cells to cytokines and alters their adhesion properties. When stimulated by interleukin (IL)-2, C77G T cells proliferated more strongly than wild-type controls and showed accelerated phosphorylation of Janus kinase (Jak1). Furthermore, C77G T cells exhibited a higher tendency to form homotypic aggregates in culture which could be enhanced significantly by antibody-mediated triggering of the variant CD45RA molecules. These data indicate that the changes in CD45 isoform combination resulting from C77G may not only affect TCR signalling but also cytokine-driven T cell responses and cellular adhesion. Altered immune responsiveness may enhance susceptibility of C77G carriers for certain diseases.
Substance P regulates macrophage inflammatory protein 3α/chemokine C-C ligand 20 (CCL20) with heme oxygenase-1 in human periodontal ligament cells
Authors: Lee S-K , Pi S-H , Kim S-H , Min K-S , Lee H-J , Chang H-S , Kang K-H , Kim H-R , Shin H-I , Lee S-K , Kim E-C
Published: July 2010

Although substance P (SP), a potent proinflammatory peptide, is involved in inflammation and immune responses, the effect of SP on the expression of macrophage inflammatory protein 3α[MIP-3α, chemokine C-C ligand 20 (CCL20)] in periodontal ligament (PDL) cells is unknown. Equally enigmatic is the link between SP, the stress protein heme oxygenase-1 (HO-1), and CCL20 production. We investigated whether SP induces the release of chemokine CCL20 from immortalized PDL (IPDL) cells, and further clarify SP-mediated pathways. We also examined the relationship between HO-1 and CCL20 by treating PDL cells with SP. Incubating IPDL cells with SP increased expression of CCL20 mRNA and CCL20 protein in a dose–time-dependent manner. Highly selective p38 and extracellular-regulated kinase 1/2 (ERK1/2) inhibitors abrogated SP-induced expression of CCL20 in IPDL cells. SP is also responsible for initiating phosphorylation of IκB, degradation of IκB and activation of nuclear factor (NF)-κB. SP induced expression of HO-1 in both a concentration- and time-dependent manner, and CCL20 reflected similar patterns. The inductive effects of SP on HO-1 and CCL20 were enhanced by HO-1 inducer hemin and the membrane-permeable guanosine 3′,5′-monophosphate (cGMP) analogue 8-bromo-cGMP. Conversely, this pathway was inhibited by the HO-1 inhibitor zinc protoporphyrin IX (ZnPP IX) and the selective inhibitor of guanylate cyclase, 1H-(1,2,4)oxadiazole(4,3-a)quinoxalin-1-one (ODQ). We report herein the pathway that connects SP along with other modulators of neuroimmunoregulation to the induction of HO-1 and the inflammatory mediator macrophage inflammatory protein (MIP)-3α/CCL20 in IPDL cells, which play an important role in the development of periodontitis or inflammation during orthodontic tooth movement.
Differential immunomodulatory properties of Bifidobacterium logum strains: relevance to probiotic selection and clinical applications
Authors: Medina M , Izquierdo E , Ennahar S , Sanz Y
Published: July 2010

Modulation of host immunity is one of the proposed benefits of the consumption of probiotics. Nonetheless, comparative studies on the immunological properties that support the selection of strains of the same species for specific health benefits are limited. In this study, the ability of different strains of Bifidobacterium longum to induce cytokine production by peripheral blood mononuclear cells (PBMCs) has been evaluated. Live cells of all B. longum strains greatly stimulated regulatory cytokine interleukin (IL)-10 and proinflammatory cytokine tumour necrosis factor (TNF)-α production. Strains of the same species also induced specific cytokine patterns, suggesting that they could drive immune responses in different directions. The probiotic strain B. longum W11 stimulated strongly the production of T helper 1 (Th1) cytokines while B. longum NCIMB 8809 and BIF53 induced low levels of Th1 cytokines and high levels of IL-10. The effects of cell-surface components obtained by sonication of B. longum strains overall confirm the effects detected by stimulation of PBMCs with live cells, indicating that these components are important determinants of the immunomodulatory activity of B. longum. Genomic DNA of some strains stimulated the production of the Th1 and pro-inflammatory cytokines, interferon (IFN)-γ and TNF-α, but not that of IL-10. None of the cell-free culture supernatants of the studied strains was able to induce TNF-α production, suggesting that the proinflammatory component of these strains is associated mainly with structural cell molecules. The results suggest that despite sharing certain features, some strains can perform a better functional role than others and their careful selection for therapeutic use is desirable.
The immunosuppressive and protective ability of glucose-regulated protein 78 for improvement of alloimmunity in β cell transplantation
Authors: Wang M , Wang P , Liu Y Q , Peng J L , Zhao X P , Wu S , He F R , Wen X , Li Y , Shen G X
Published: July 2010

An insulinoma cell line, NIT-1, transfected with glucose-regulated protein 78 (GRP78) was established, namely NIT-GRP78, and used to study the immunosuppressive and protective ability of GRP78. In extended cytotoxic T lymphocyte (CTL) killing assay, NIT-1-primed lymphocytes were more cytotoxic in killing β cells than NIT-GRP78-primed lymphocytes. Severe necrosis was observed only when the NIT-1-primed lymphocytes were cultured with NIT-1 β cells, but not with NIT-GRP78 cells. In addition, an increase of interleukin (IL)-4 secretion from β cell-primed splenocytes when GRP78 presence was observed in cytokine enzyme-linked immunosorbent assay (ELISA). Diabetic mice reached normoglycaemia promptly and gained weight after transplantation of either NIT-1 or NIT-GRP78 cells. However, the recipient mice transplanted with NIT-GRP78 cells lived much longer than those recipients transplanted with NIT-1 cells, which was due apparently to prolonged insulin production by the transplanted NIT-GRP78 cells. In fact, we observed a significant increase of insulin concentration after glucose stimulation of diabetic mice received NIT-GRP78 cells at day 7 post-transplantation. From the results we propose that GRP78 could have a dual function in both protecting NIT-1 cells from CTL-mediated lysis and stimulating a population of T helper 2 cells to down-regulate the immune response to the transplanted β cells.
High-fat diet modulates non-CD1d-restricted natural killer T cells and regulatory T cells in mouse colon and exacerbates experimental colitis
Authors: Ma X , Torbenson M , Hamad A R A , Soloski M J , Li Z
Published: July 2010

Environmental factors such as diet are known to play important roles in inflammatory bowel disease (IBD). Epidemiological studies have indicated that a high-fat diet is a risk factor for IBD. In addition, the balance between effector T cells (Teff) and regulatory T cells (Treg) contributes to the pathogenesis of mucosal inflammation. The aim of this study was to understand the mechanisms by which a high-fat diet can regulate susceptibility to intestinal inflammation. Wild-type C57BL/6 mice were fed either a commercial high-fat diet or a normal diet, then exposed to dextran sulphate sodium (DSS) to induce colonic inflammation. Intraepithelial lymphocytes (IEL) were isolated from the colon, and their phenotype and cytokine profile were analysed by flow cytometry. Mice receiving the high-fat diet were more susceptible to DSS-induced colitis. They had higher numbers of non-CD1d-restricted natural killer (NK) T cells in the colonic IEL, when compared to mice fed a normal diet. These cells expressed tumour necrosis factor (TNF)-α and interferon (IFN)-γ, which are up-regulated by high-fat diets. Mice fed the high-fat diet also had decreased levels of colonic Treg. Depletion of colonic NK T cells or adoptive transfer of Treg reduced the DSS colitis in these mice, and reduced the colonic expression of TNF-α and IFN-γ. We conclude that a high-fat diet can increase non-CD1d-restricted NK T cells and decrease Treg in the colonic IEL population. This altered colonic IEL population leads to increased susceptibility to DSS-induced colitis. This effect may help to explain how environmental factors can increase the susceptibility to IBD.
Natural human antibodies to pneumococcus have distinctive molecular characteristics and protect against pneumococcal disease
Authors: Baxendale H E , Johnson M , Stephens R C M , Yuste J , Klein N , Brown J S , Goldblatt D
Published: July 2010

The molecular and functional characteristics of natural antibody from the preimmune repertoire have not been explored in detail in man. We describe seven human IgM monoclonal antibodies selected on the basis of pneumococcal polysaccharide binding that share both molecular and functional characteristics with natural antibody, suggesting a common B cell lineage origin. Unlike class-switched antibodies, which are serotype-specific, the antibodies were polyreactive and bound all pneumococcal polysaccharide capsular serotypes tested. Some bound endogenous antigens, including blood group antigens and intermediate filament proteins. All the antibodies used unmutated heavy chain V (IGHV) that are expressed at an increased frequency in the elderly and in the preimmune repertoire. The CDR3 was characterized by long length (mean aa 18·4 (±4·2) and selective use of IGHD6 (P < 0·001) and IGHJ6 (P < 0·01) family genes. The clones expressing IGHV1-69 and IGHV 3-21 provided significant passive protection against invasive pneumococcal disease in vivo.
T cell receptor Vβ repertoire of T lymphocytes and T regulatory cells by flow cytometric analysis in healthy children
Authors: McLean-Tooke A , Barge D , Spickett G P , Gennery A R
Published: July 2010

Evaluation of the T cell receptor (TCR) Vβ repertoire by flow cytometric analysis has been used for studying the T cell compartments for diseases in which T cells are implicated in the pathogenesis. For the interpretation of these studies information is needed about Vβ usage in healthy individuals and there are few data for normal usage in paediatric populations. We examined the T lymphocyte (sub)populations in 47 healthy controls (age range: 3 months−16 years). We found non-random Vβ usage with skewed reactivity of some families towards CD4+ or CD4– T cells. Importantly, there appeared to be no significant change in Vβ usage according to age group. Some controls showed expansions in some Vβ families, although incidence of such expansions was low. We went on to examine the repertoire of CD4+CD25Bright T regulatory cells in 25 healthy controls. We found overlapping quantitative usage for each of the Vβ families between CD4+CD25– and CD4+CD25Bright T cells. However, there was a significant preferential usage for five Vβ families and decreased usage of two Vβ families in the CD4+CD25Bright T cells, suggesting that although they overlap there may be subtle but important differences in the TCR repertoire of T regulatory cells.
Serum levels of immunoglobulins (IgG, IgA, IgM) in a general adult population and their relationship with alcohol consumption, smoking and common metabolic abnormalities
Authors: Gonzalez-Quintela A , Alende R , Gude F , Campos J , Rey J , Meijide L M , Fernandez-Merino C , Vidal C
Published: July 2010

The present study investigated serum immunoglobulin (Ig) concentrations in relation to demographic factors, common habits (alcohol consumption and smoking) and metabolic abnormalities in an adult population-based survey including 460 individuals. Serum levels of interleukin (IL)-6, a marker of inflammation, were also determined. After adjusting for confounders, male sex was associated positively with IgA levels and negatively with IgM levels. Age was associated positively with IgA and IgG levels. Smoking was associated negatively with IgG levels. Heavy drinking was associated positively with IgA levels. Metabolic abnormalities (obesity and metabolic syndrome) were associated positively with IgA levels. Abdominal obesity and hypertriglyceridaemia were the components of metabolic syndrome associated most strongly with serum IgA. Heavy drinkers with metabolic syndrome showed particularly high serum IgA levels. Serum IL-6 levels were correlated positively with IgA and IgG concentrations. It is concluded that sex, age, alcohol consumption, smoking and common metabolic abnormalities should be taken into account when interpreting serum levels of IgA, IgG and IgM.
Persistent of respiratory syncytial virus in human dendritic cells and influence of nitric oxide
Authors: Hobson L , Everard M L
Published: July 2010

The annual epidemics of respiratory syncytial virus (RSV) infection are probably explained by poor herd immunity and the existence of a dormant reservoir of virus that is activated by an unknown trigger. The virus causes particular problems in infants, the elderly and patients with chronic obstructive airways disease (COPD). During two consecutive winters, human monocyte-derived dendritic cells (DCs) were exposed on a single occasion to one of two forms of RSV labelled with a fluorescent expresser genes (rgRSV or rrRSV) during the epidemic season. The cultures were maintained for many months, with fresh DCs being added at monthly intervals. The cultures were variously exposed to 600 parts per billion (ppb) nitric oxide for 15 min, nitric oxide (NO) donors and NO inhibitors outside the RSV epidemic season. The pattern of productive infection of DCs in vitro appeared to parallel the natural epidemics, in that DCs exhibited evidence of viral replication and productive infection only as manifested by intracellular fluorescence and infection of HeLa cells during the RSV epidemic season. When the long-term cultures were exposed to the above agents outside the RSV epidemic season there was again evidence of vigorous replication and productive infection, as shown by the reappearance of fluorescence and productive infection of HeLa cells. The results indicate that RSV may remain dormant in dendritic cells for prolonged periods and that replication appears to be activated by suppression of endogenous NO production. These observations may be key to our understanding of the mechanisms contributing to the annual epidemics of RSV infection.
Imatinib mesylate, a new kid on the block for the treatment of anti-neutrophil cytoplasmic autoantibodies-associated vasculitis?
Authors: Kälsch A-I , Soboletzki M , Schmitt W H , van der Woude F J , Hochhaus A , Yard B A , Birck R
Published: July 2010

Persistent T cell activation is a common finding in anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated systemic vasculitis (AAV) patients. Because imatinib, a selective inhibitor of the ABL, ARG, PDGFR and c-KIT tyrosine kinases, inhibits T cell activation, this study was conducted to evaluate the potential use of imatinib for the treatment AAV patients refractory to conventional therapy. In particular, we investigated the inhibition of T cell activation by this drug and its efficacy on activated T cells from anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated systemic vasculitides (AASV) patients. T cell stimulation has been induced by anti-CD3/anti-CD28 antibodies or by phorbol myristate acetate (PMA)/ionomycin. T cell proliferation was analysed by tritiumthymidine incorporation. Cell cycle progression was determined by propidium iodide staining using fluorescence activated cell sorter (FACS) analysis and by RNAse protection assay (RPA). Cytokine levels were assessed by enzyme-linked immunosorbent assay. T cell proliferation was inhibited significantly by imatinib, due most probably to cell cycle arrest in the G1-phase. This was paralleled by inhibition in the expression of cyclin-dependent kinases 1 and 2 mRNA. The expression of CD25 in naive and memory T cells was decreased significantly by imatinib in activated T cells. Similarly, conversion from naive to memory T cells after T cell activation was impaired by imatinib. Imatinib did not influence interleukin-2 and tumour necrosis factor-α production but increased interferon-γ production. These observed effects of imatinib were similar in T cells from AASV patients and from healthy individuals. Imatinib might be an alternative therapeutical option for AASV patients refractory to conventional therapy.
Factors associated with CD4 lymphocyte counts in HIV-negative Senegalese individuals
Authors: Mair C , Hawes S E , Agne H D , Sow P S , N'doye I , Manhart L E , Fu P L , Gottlieb G S , Kiviat N B
Published: July 2010

CD4+ lymphocytes are a primary target of the human immunodeficiency virus (HIV), and CD4 counts are one of the factors used to measure disease progression in HIV-positive individuals. CD4 counts vary in uninfected individuals and across populations due to a variety of demographic, environmental, immunological and genetic factors that probably persist throughout the course of HIV infection. This study sought to determine reference levels and identify factors that influence lymphocyte counts in 681 HIV-uninfected adults in Senegal, where residents are exposed to a variety of infectious diseases and other conditions that may affect CD4 counts. Lymphocyte counts were assessed in commercial sex workers, symptomatic men and women presenting to the University of Dakar infectious disease clinic for out-patient care and women seeking family planning services. CD4 and CD3 lymphocyte counts differed between the four study groups (P < 0·01). Men had the lowest mean CD4 count (711·6 cells/μl), while commercial sex workers had the highest levels (966·0 cells/μl). After adjustment for age and other behavioural and clinical factors, the difference in CD4 counts between the three groups of women did not remain. However, both gender and smoking were associated independently with CD4 counts, as men maintained lower mean CD4 counts (β = −156·4 cells/μl, P < 0·01) and smokers had higher mean CD4 counts (β = 124·0 cells/μl, P < 0·01) than non-smokers in multivariable analyses. This study is the first to explore factors that may influence CD4 levels in Senegal and to estimate baseline CD4 levels among HIV-negatives, information that may guide clinicians in interpreting CD4 counts.
The Wistar Bonn Kobori rat, a unique animal model for autoimmune pancreatitis with extrapancreatic exocrinopathy
Authors: Sakaguchi Y , Inaba M , Tsuda M , Quan G K , Omae M , Ando Y , Uchida K , Okazaki K , Ikehara S
Published: July 2010

The male Wistar Bonn/Kobori (WBN/Kob) rat is known to be a unique animal model for chronic pancreatitis with widely distributed fibrosis and degeneration of parenchyma because of the infiltration of lymphocytes. In this report, we show that female (but not male) rats develop dacryoadenitis at 3 months of age, and that both male and female WBN/Kob rats develop sialoadenitis, thyroiditis, sclerotic cholangitis and tubulointerstitial nephritis over 18 months of age. The infiltration of CD8+ cells and the deposits of tissue-specific IgG2b were observed in the injured pancreas and lachrymal glands. Furthermore, the number of regulatory T cells (defined as CD4+ Forkhead box P3+ cells) decreased in the periphery of both male and female WBN/Kob rats, suggesting that the onset of these diseases is attributable, at least, to the failure in the maintenance of peripheral immune tolerance. These features show clearly that WBN/Kob rats are a useful animal model for autoimmune pancreatitis and Sjøgren-like syndrome or multi-focal fibrosclerosis in humans. We also show that these autoimmune diseases can be prevented by a newly devised strategy of bone marrow transplantation (BMT) in which bone marrow cells are injected directly into the bone marrow cavity: intrabone marrow–BMT.
Effect of taurine on oxidative stress and apoptosis-related protein expression in trinitrobenzene sulphonic acid-induced colitis
Authors: Giriş M , Depboylu B , Doğru-Abbasoğlu S , Erbil Y , Olgaç V , Alış H , Aykaç-Toker G , Uysal M
Published: July 2010

Ulcerative colitis (UC) is a multi-factorial inflammatory disease of the colon and rectum. The present study was undertaken to investigate the effect of taurine, an anti-oxidant amino acid, on oxidative stress and the expression of apoptosis-related proteins, pro-apoptotic Bax and anti-apoptotic B cell lymphoma-2 (Bcl-2) in colon tissue in rats with 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. Rats received taurine (1·5% w/v) in drinking water for 15 days before and 15 days after administration of TNBS solution. Then, colonic myeloperoxidase (MPO) activity, malondialdehyde (MDA) and glutathione (GSH) levels, and Bax and Bcl-2 expression were measured. TNBS-induced colitis caused significantly increased MPO activity and MDA levels and decreased GSH levels in colon tissue compared to controls. Increase in Bax expression and decrease in Bcl-2 expression were detected in colon of rats with TNBS-induced colitis. Taurine treatment was associated with amelioration in macroscopic and microscopic colitis scores, decreased colonic MPO activity and MDA levels and increased GSH levels in TNBS-induced colitis. In addition, taurine reduced the expression of Bax and prevented the loss of Bcl-2 proteins in colon tissue of rats with TNBS-induced colitis. The results of this study show that taurine administration may exert beneficial effects in UC by decreasing inflammatory reactions, oxidative stress and apoptosis.
Common studied polymorphisms do not affect plasma cytokine levels upon endotoxin exposure in humans
Authors: Taudorf S , Krabbe K S , Berg R M G , Møller K , Pedersen B K , Bruunsgaard H
Published: July 2010

The aim of this study was to investigate to what extent single nucleotide polymorphisms (SNPs) in promoter regions of genes of Toll-like receptor (TLR)-4, tumour necrosis factor (TNF)-α, interleukin (IL)-18, interferon (IFN)-γ, IL-6 and IL-10 affect the cytokine response during a controlled low-grade inflammatory response in vivo. Two hundred healthy young male volunteers were genotyped, and cytokine levels were measured in response to a low-dose intravenous bolus of Escherichia coli endotoxin. No association was detected between SNPs (TLR-4299, TLR-4399, TNF-308, IL-18-137, IL-18-607, IFN-γ+874, IL-6-174, IL-10-592 and IL-10-1082) and endotoxin-induced changes in plasma levels of TNF-α, IL-6 and IL-10. IL-18 levels were unaffected by endotoxin. In conclusion, the investigated SNPs did not affect endotoxin-induced low-grade cytokine production of TNF-α, IL-6, IL-18 or IL-10 in healthy young men. Previous reports of a major heritability factor in the inflammatory response may be due to other target genes or effects in older age groups or women.
Innate lymphocyte and dendritic cell cross-talk: a key factor in the regulation of the immune response
Authors: Reschner A , Hubert P , Delvenne P , Boniver J , Jacobs N
Published: July 2010

Dendritic cells (DC) are specialized in the presentation of antigens and the initiation of specific immune responses. They have been involved recently in supporting innate immunity by interacting with various innate lymphocytes, such as natural killer (NK), NK T or T cell receptor (TCR)-γδ cells. The functional links between innate lymphocytes and DC have been investigated widely and different studies demonstrated that reciprocal activations follow on from NK/DC interactions. The cross-talk between innate cells and DC which leads to innate lymphocyte activation and DC maturation was found to be multi-directional, involving not only cell–cell contacts but also soluble factors. The final outcome of these cellular interactions may have a dramatic impact on the quality and strength of the down-stream immune responses, mainly in the context of early responses to tumour cells and infectious agents. Interestingly, DC, NK and TCR-γδ cells also share similar functions, such as antigen uptake and presentation, as well as cytotoxic and tumoricidal activity. In addition, NK and NK T cells have the ability to kill DC. This review will focus upon the different aspects of the cross-talk between DC and innate lymphocytes and its key role in all the steps of the immune response. These cellular interactions may be particularly critical in situations where immune surveillance requires efficient early innate responses.
The tumour suppressor gene p53 modulates the severity of antigen-induced arthritis and the systemic immune response
Authors: Leech M , Xue J R , Dacumos A , Hall P , Santos L , Yang Y , Li M , Kitching A R , Morand E F
Published: July 2010

p53 is a transcription factor with a well-described role in the induction of apoptosis and cell cycle arrest as part of a protective response to a variety of stressful stimuli. Expansion of inflamed tissue in rheumatoid arthritis has been related to the loss of functioning p53, and the severity of collagen-induced arthritis is increased in p53–/– mice. Our objective was to assess the role of p53 in a model of adaptive immunity, antigen-induced arthritis (AIA). AIA was induced in p53–/– and wild-type mice by priming with methylated bovine serum albumin followed by intra-articular challenge. Severity of arthritis was assessed using a standardized scoring system and synovial apoptosis was detected by TdT-mediated biotin-dUTP nick-end labelling. Splenocyte proliferation was measured by [H3] incorporation and interferon (IFN)-γ release. Splenocyte viability was assessed using Titreglow. Splenic T cell activation status was assessed by flow cytometry. Serum cytokines were measured using enzyme-linked immunosorbent assay. Increased severity of AIA in p53–/– mice was associated with decreased synovial apoptosis and with increased delayed-type hypersensitivity response, increased mitogen and antigen-induced splenocyte proliferation and increased IFN-γ release in p53–/– mice compared with wild-type mice. Antigen-specific immunoglobulin responses were equivalent in both groups. Splenocyte viability was increased in p53–/– mice but T cell apoptosis was equivalent. T cell activation markers were increased in p53–/– mice compared with wild-type mice. Lipopolysaccharide-induced tumour necrosis factor release was increased in p53–/– mice with a trend to increased interleukin-6 in p53–/– mice compared with littermates. p53 is involved in the modulation of adaptive and innate immune responses relevant to arthritis models and is also involved in the modulation of severity of AIA by both cell-cycle dependent and cell-cycle-independent mechanisms.
Possible role of natural killer cells in pemphigus vulgaris − preliminary observations
Authors: Stern J N H , Keskin D B , Barteneva N , Zuniga J , Yunis E J , Ahmed A R
Published: July 2010

Pemphigus vulgaris (PV) is an autoimmune blistering disease that affects the skin and multiple mucous membranes, and is caused by antibodies to desmoglein (Dsg) 1 and 3. Natural killer (NK) cells have a role in autoimmunity, but their role in PV is not known. NK cells in the peripheral blood leucocytes (PBL) of 15 untreated Caucasian patients with active PV were studied and compared with healthy controls for the expression of major histocompatibility complex (MHC) class II and co-stimulatory molecules. CD56+ CD16- CD3- NK or CD56+ CD16+ CD3- NK cells from the PBL of PV patients co-express MHC class II and co-stimulatory molecule B7-H3 without exogenous stimulation. CD4+ T cells from the PBL and perilesional skin of PV patients were co-cultured with CD56+ CD3- NK cells from the PBL of the same patients; in the presence of Dsg3 peptides underwent statistically significant proliferation, indicating that NK cells functioned as antigen-presenting cells. Supernatants from these co-cultures and serum of the same patients with active PV had statistically significantly elevated levels of interleukin (IL)-6, IL-8 and interferon-γ, compared with controls indicating that the NK cells stimulated CD4+ T cells to produce proinflammatory cytokines. In these experiments, we present preliminary evidence that NK cells may play a role in the pathobiology of PV.
Clinical Immunology Review Series: An approach to the patient with recurrent superficial abscesses
Authors: Johnston S L
Published: July 2010

Patients may be referred to the immunology clinic for investigation of recurrent superficial abscess formation. In the majority of adult patients this clinical presentation does not equate with an underlying primary immune deficiency. Nevertheless, recurrent mucocutaneous abscesses can be associated with significant morbidity and long-term complications, including scarring and fistula formation, and may be associated with underlying immune-mediated disease. This review sets out an approach to the patient with recurrent superficial abscesses, focusing on the differential diagnoses, investigation and management of both the common causes and those associated with specific immune deficiency.
Adrenomedullin suppresses tumour necrosis factor alpha-induced CXC chemokine ligand 10 production by human gingival fibroblasts
Authors: Hosokawa I , Hosokawa Y , Ozaki K , Nakae H , Matsuo T
Published: July 2010

Periodontal disease is an inflammatory disorder characterized by the involvement of chemokines that are important for the recruitment of leucocytes. Several cytokines, including tumour necrosis factor alpha (TNF-α), are involved in regulating levels of chemokines in periodontal disease. CXC chemokine ligand 10 (CXCL10) is a chemokine related to the migration of T helper 1 cells. In this study, we examined CXCL10 expression in human gingival fibroblasts (HGFs). Moreover, we investigated the effects of adrenomedullin (AM), which is a multi-functional regulatory peptide, on the production of CXCL10 by HGFs. We revealed that TNF-α stimulation induced CXCL10 production by HGFs. HGFs expressed AM and AM receptors, calcitonin-receptor-like receptor (CRLR) and receptor-activity-modifying protein (RAMP) 2, mRNAs constitutively. AM treatment supressed CXCL10 production by TNF-α-stimulated HGFs. Moreover, we elucidated that AM produced by HGFs inhibited CXCL10 production by HGFs, because AM antagonist enhanced CXCL10 production by HGFs. TNF-α treatment enhanced CRLR and RAMP2 mRNA expression in HGFs. Furthermore, AM is expressed in human periodontal tissues, including both inflamed and clinically healthy tissues. These results suggest that the CXCL10 produced by HGFs may be involved in the migration of leucocytes into inflamed tissues and related to exacerbation of periodontal disease. AM might be a therapeutic target of periodontal disease, because AM can inhibit CXCL10 production by HGFs.
99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Darwinian medicine and the ‘hygiene’ or ‘old friends’ hypothesis
Authors: Rook G A W
Published: July 2010

The current synthesis of the ‘hygiene hypothesis’ suggests that the recent increase in chronic inflammatory disorders is at least partly attributable to immunodysregulation resulting from lack of exposure to microorganisms that have evolved an essential role in the establishment of the immune system. This document provides a background for discussion of the following propositions. The essential role of these organisms is an example of ‘evolved dependence’.The most relevant organisms are those that co-evolved with mammals, and already accompanied early hominids in the Paleolithic.More recently evolved ‘childhood infections’ are not likely to have evolved this role, and recent epidemiology supports this contention.This mechanism is interacting with other modern environmental changes that also lead to enhanced inflammatory responses [inappropriate diet, obesity, psychological stress, vitamin D deficiency, pollution (dioxins), etc.].The range of chronic inflammatory disorders that is affected is potentially larger than usually assumed [allergies, autoimmunity, inflammatory bowel disease, but also vascular disease, some cancers, depression/anxiety (when accompanied by raised inflammatory cytokines), and perhaps neurodegenerative disorders and type 2 diabetes].
99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Innate immune responses in plants
Authors: Schulze-Lefert P
Published: July 2010

Plants rely exclusively upon mechanisms of innate immunity. Current concepts of the plant innate immune system are based largely on two forms of immunity that engage distinct classes of immune receptors. These receptors enable the recognition of non-self structures that are either conserved between members of a microbial class or specific to individual strains of a microbe. One type of receptor comprises membrane-resident pattern recognition receptors (PRRs) that detect widely conserved microbe-associated molecular patterns (MAMPs) on the cell surface. A second type of mainly intracellular immune sensors, designated resistance (R) proteins, recognizes either the structure or function of strain-specific pathogen effectors that are delivered inside host cells. Phytopathogenic microorganisms have evolved a repertoire of effectors, some of which are delivered into plant cells to sabotage MAMP-triggered immune responses. Plants appear to have also evolved receptors that sense cellular injury by the release and perception of endogenous damage-associated molecular patterns (DAMPs). It is possible that the integration of MAMP and DAMP responses is critical to mount robust MAMP-triggered immunity. This signal integration might help to explain why plants are colonized in nature by remarkably diverse and seemingly asymptomatic microbial communities.
99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Neonatal immune function and vaccine responses in children born in low-incomeversushigh-income countries
Authors: Van Den Biggelaar A H J , Holt P G
Published: July 2010

There is increasing evidence that the functional state of the immune system at birth is predictive of the kinetics of immune maturation in early infancy. Moreover, this maturation process can have a major impact on early vaccine responses and can be a key determinant of risk for communicable and non-communicable diseases in later life. We hypothesize that environmental and genetic factors that are often typical for poor-resource countries may have an important impact on prenatal immune development and predispose populations in low-income settings to different vaccine responses and disease risks, compared to those living in high-income countries. In this paper we aimed to summarize the major differences between neonatal and adult immune function and describe what is known so far about discrepancies in immune function between newborns in high- and low-income settings. Further, we discuss the need to test the immunological feasibility of accelerated vaccination schedules in high-risk populations and the potential of variation in disease specific and non-specific vaccine effects.
The ‘hygiene hypothesis’ for autoimmune and allergic diseases: an update
Authors: Okada H , Kuhn C , Feillet H , Bach J-F
Published: July 2010

According to the ‘hygiene hypothesis’, the decreasing incidence of infections in western countries and more recently in developing countries is at the origin of the increasing incidence of both autoimmune and allergic diseases. The hygiene hypothesis is based upon epidemiological data, particularly migration studies, showing that subjects migrating from a low-incidence to a high-incidence country acquire the immune disorders with a high incidence at the first generation. However, these data and others showing a correlation between high disease incidence and high socio-economic level do not prove a causal link between infections and immune disorders. Proof of principle of the hygiene hypothesis is brought by animal models and to a lesser degree by intervention trials in humans. Underlying mechanisms are multiple and complex. They include decreased consumption of homeostatic factors and immunoregulation, involving various regulatory T cell subsets and Toll-like receptor stimulation. These mechanisms could originate, to some extent, from changes in microbiota caused by changes in lifestyle, particularly in inflammatory bowel diseases. Taken together, these data open new therapeutic perspectives in the prevention of autoimmune and allergic diseases.
The effect of maturity on the texture of the testa and cotyledon of peas (Pisum sativum)
Authors: WAGER HAROLD G. , PORTER F. A. E.
Published: July 2010

The textures of the separated testa and cotyledon of peas both when raw and cooked were measured with a small penetrometer over a wide range of maturity. The values for the raw testa rose little with increase in age but the cooked testa and the raw and cooked cotyledon all rose markedly. There were no significant differences in six varieties tested. It is argued that instruments predicting the texture of the cooked pea from the raw must measure the hardness of the cotyledon.
Compositional analysis of liquid egg products using infrared transmission spectroscopy
Authors: OSBORNE B. G. , BARRETT G. M.
Published: July 2010

Calibration equations have been developed for the measurement of protein, total lipid and total solids content of liquid egg products using infrared transmission spetroscopy and the technique enables all these analyses to be carried out in under 20 min. Multiple correlation coefficients of 0.982, 0.988 and 0.997 and residual standard deviations of 0.37, 0.66 and 1.06% respectively were obtained for the infrared method compared with standard procedures. The results for total solids was not significantly different from that obtained by regression of total solids on combined protein and total lipid, all three determined by standard methods.
Hard‐to‐cook phenomenon in common beans‐ influence of growing location and hardening procedures
Authors: PAREDES‐LÓPEZ O. , REYES‐MORENO C. , MONTES‐RIVERA R. , CARABEZ‐TREJO A.
Published: July 2010

Two accelerated hardening procedures (storage for up to 4 months, and soaking in acetate buffer for up to 5 h) for testing beans were examined and compared, so that new cultivars prone to the hard‐to‐cook (HTC) defect may be identified. Bean hardness was measured by means of the Mattson bean cooker, and by measuring puncture force. Two imporant common bean (Phaseolis vulgaris)cultivars were grown in two locations differing in soil Ca and Mg content. Those from the high Ca site had longer cooking times, which increased more rapidly on accelerated storage and in the soaking tests. The results of this preliminary study suggest that the acetate soak hardening procedure is worthy of further investigation as the basis of a rapid test for the presence of the hard‐to‐cook defect in new cultivars.
Effect of natural copper chelating compounds on the pro‐oxidant activity of ascorbic acid in steam‐cooked ground fish
Authors: RAMANATHAN LALINI , DAS NAGARATHAM P.
Published: July 2010

The antioxidative effects of several natural polyphenolic substances on ascorbic acid‐induced lipid oxidation, measured as thiobarbituric acid‐reactive substances (TBARS) was studied in steam‐cooked ground fish. Those natural polyphenolic compounds that were potent antioxidants in the presence of ascorbic acid were also effective inhibitors of copper‐induced oxidation of ascorbic acid. the order of potency of the natural products was: tannic acid ∼ ellagic acid > myricetin > n‐Propyl gallate > fisetin > quercetin ° luteolin > gallic acid. It is likely that the potent flavonoids inhibited lipid oxidation in ascorbic acid pre‐treated cooked ground fish by reducing the rate of copper‐induced oxidation of ascorbic acid, thereby decreasing the production of free radicals. Flavonoids are able to exert antioxidative potential due to their free radical scavenging and metal chelating properties.
Evaluation of the Antioxidant Properties of the Brazilian Cerrado Fruit Annona crassiflora (Araticum)
Authors: Roesler Roberta , Malta Luciana G. , Carrasco Luciana C. , Pastore Gláucia
Published: July 2010

Annona crassiflora, known commonly as araticum, is an exotic tropical fruit consumed mainly by native people of the Brazilian Cerrado (2nd biggest biome of Brazil). In this study, pulp, seed, and peel of slight ripe and overripe fruits were extracted using ethanol and water. The extracts showed high content of total phenols and were screening for their potential as antioxidants using the in vitro model 1,1‐ dipheniyl‐2‐picryl hydrazyl (DPPH). The ethanol extracts of peel and seeds showed IC50 of 48.82 μg/mL and 31.14 μg/mL, respectively, for the slightly ripe fruits. As the ethanolic fractions of araticum showed the highest antioxidant activity, they were selected for testing of its effect on lipid peroxidation. The ethanolic extracts of slightly ripe fruits showed IC50 of 4.44 μg/mL, 1.72 μg/mL, and 8.62 μg/mL for the peel, seed, and pulp, respectively. This is the 1st report on the antioxidant properties of the extracts of araticum. Owing to these properties, the studies can be further extending to exploit them for their possible application as natural antioxidant for cosmetic, supplements, and functional ingredients for food products.
Habitat availability does not explain the species richness patterns of European lentic and lotic freshwater animals
Authors: Dehling D. Matthias , Hof Christian , Brändle Martin , Brandl Roland
Published: July 2010

Aim  In Europe, the relationships between species richness and latitude differ for lentic (standing water) and lotic (running water) species. Freshwater animals are highly dependent on suitable habitat, and thus the distribution of available habitat should strongly influence large‐scale patterns of species richness. We tested whether habitat availability can account for the differences in species richness patterns between European lentic and lotic freshwater animals.

Location  Europe.

Methods  We compiled occurrence data of 1959 lentic and 2445 lotic species as well as data on the amount of lentic and lotic habitats across 25 pre‐defined biogeographical regions of European freshwaters. We used the range of elevation of each region as a proxy for habitat diversity. We investigated the relationships between species richness, habitat availability and habitat diversity with univariate and multiple regression analyses.

Results  Species richness increased with habitat availability for lentic species but not for lotic species. Species richness increased with elevational range for lotic species but decreased for lentic species. For both groups, neither habitat availability nor diversity could account for previously reported latitudinal patterns in species richness. For lotic species, richness declined with latitude, whereas there was no relationship between habitat availability and latitude. For lentic species, richness showed a hump‐shaped relationship with latitude, whereas available habitat increased with latitude.

Main conclusions  Habitat availability and diversity are poor predictors of species richness of the European freshwater fauna across large scales. Our results indicate that the distributions of European freshwater animals are probably not in equilibrium and may still be influenced by history, namely the recurrent European glaciations and possible differences in post‐glacial recolonization. The distributions of lentic species appear to be closer to equilibrium than those of lotic species. This lends further support to the hypothesis that lentic species have a higher propensity for dispersal than lotic species.
Phylogeographic patterns of genetic diversity in eastern Mediterranean water frogs were determined by geological processes and climate change in the Late Cenozoic
Authors: Akın Çiğdem , Can Bilgin C. , Beerli Peter , Westaway Rob , Ohst Torsten , Litvinchuk Spartak N. , Uzzell Thomas , Bilgin Metin , Hotz Hansjürg , Guex Gaston‐Denis , Plötner Jörg
Published: July 2010

Aim  Our aims were to assess the phylogeographic patterns of genetic diversity in eastern Mediterranean water frogs and to estimate divergence times using different geological scenarios. We relate divergence times to past geological events and discuss the relevance of our data for the systematics of eastern Mediterranean water frogs.

Location  The eastern Mediterranean region.

Methods  Genetic diversity and divergence were calculated using sequences of two protein‐coding mitochondrial (mt) genes: ND2 (1038 bp, 119 sequences) and ND3 (340 bp, 612 sequences). Divergence times were estimated in a Bayesian framework under four geological scenarios representing alternative possible geological histories for the eastern Mediterranean. We then compared the different scenarios using Bayes factors and additional geological data.

Results  The extensive genetic diversity in mtDNA divides eastern Mediterranean water frogs into six main haplogroups (MHGs). Three MHGs were identified on the Anatolian mainland; the most widespread MHG with the highest diversity is distributed from western Anatolia to the northern shore of the Caspian Sea, and includes the type locality of Pelophylax ridibundus. The other two Anatolian MHGs are restricted to south‐eastern Turkey, occupying localities west and east of the Amanos mountain range. One of the remaining three MHGs is restricted to Cyprus; the second, to the Levant; and the third was found in the distribution area of European lake frogs (P. ridibundus group), including the Balkans.

Main conclusions  Based on geological evidence and estimates of genetic divergence we hypothesize that the water frogs of Cyprus have been isolated from the Anatolian mainland populations since the end of the Messinian salinity crisis (MSC), that is, since c. 5.5–5.3 Ma, while our divergence time estimates indicate that the isolation of Crete from the mainland populations (Peloponnese, Anatolia) probably pre‐dates the MSC. The observed rates of divergence imply a time window of c. 1.6–1.1 million years for diversification of the largest Anatolian MHG; divergence between the two other Anatolian MHGs may have begun about 3.0 Ma, apparently as a result of the uplift of the Amanos Mountains. Our mtDNA data suggest that the Anatolian water frogs and frogs from Cyprus represent several undescribed species.