bluuebunny/crossref_metadata_2025_split huggingface dataset:
Actinobacillus actinomycetemcomitansY4 capsular polysaccharide induces IL-1β mRNA expression through the JNK pathway in differentiated THP-1 cells
Authors: Iwata T , Mitani A , Ishihara Y , Tanaka S , Yamamoto G , Kikuchi T , Naganawa T , Matsumura Y , Suga T , Koide M , Sobue T , Suzuki T , Noguchi T 
Published: July 2005

SummaryCapsular polysaccharide from Actinobacillus actinomycetemcomitans Y4 (Y4 CP) induces bone resorption in a mouse organ culture system and osteoclast formation in mouse bone marrow cultures, as reported in previous studies. We also found that Y4 CP inhibits the release of interleukin (IL)-6 and IL-8 from human gingival fibroblast (HGF). Thus Y4 CP induces various responses in localized tissue and leads to the secretion of several cytokines. However, the effects of Y4 CP on human monocytes/macrophages are still unclear. In this study, THP-1 cells, which are a human monocytic cell line, were stimulated with Y4 CP, and we measured gene expression in inflammatory cytokine and signal transduction pathways. IL-1β and tumour necrosis factor (TNF)-α mRNA were induced from Y4 CP-treated THP-1 cells. IL-1β mRNA expression was increased according to the dose of Y4 CP, and in a time-dependent manner. IL-1β mRNA expression induced by Y4 CP (100 µg/ml) was approximately 7- to 10-fold greater than that in the control by real-time PCR analysis. Furthermore, neither PD98059, a specific inhibitor of extracellular signal-regulated kinase nor SB203580, a specific inhibitor of p38 kinase prevented the IL-1β expression induced by Y4 CP. However, JNK Inhibitor II, a specific inhibitor of c-Jun N-terminal kinase (JNK) prevented the IL-1β mRNA expression induced by Y4 CP in a concentration-dependent manner. These results indicate that Y4 CP-mediated JNK pathways play an important role in the regulation of IL-1β mRNA. Therefore, Y4 CP-transduced signals for IL-1β induction in the antibacterial action of macrophages may provide a therapeutic strategy for periodontitis.
Possible role of autoantibodies against nephrin in an experimental model of chronic graft-versus-host disease
Authors: Nagahama K , Maru K , Kanzaki S , Chai H L , Nakai T , Miura S , Yamaguchi A , Yamanaka S , Nagashima Y , Aoki I 
Published: July 2005

SummaryNephrin, a product of the NPHS1 gene, is a component of the slit diaphragms that are found between glomerular foot processes and is a crucial element for glomerular filtration barrier. Recently, nephrin has been focused in a number of studies of proteinuria development including various types of acquired glomerular diseases including minimal change nephrotic syndrome and membranous nephropathy. However, the precise role of nephrin in such acquired glomerular diseases is still unknown. To analyse the role of nephrin further, two kinds of anti-nephrin antibodies were raised in the rabbits and applied to an experimental mouse model of chronic graft-versus-host disease, in which (C57BL/10 × DBA/2) F1 mice developed clinically apparent severe proteinuria with significant glomerular lesions 7 weeks after parental DBA/2 cell transfer. Antibody-sandwich ELISA detected anti-nephrin antibodies during week 2 to week 6, with the peak at week 2 or week 4. Colocalization of nephrin and IgG on week 4, week 6, and week 8 was revealed by confocal microscopic analysis, suggesting that in situ immune complex formation with nephrin in glomerular lesion. Taken together, it seems to be suggested nephrin and its autoantibody have a certain role in the development of glomerular lesion in our model mice.
Strain-specific differences in perivascular inflammation in lungs in two murine models of allergic airway inflammation
Authors: Singh B , Shinagawa K , Taube C , Gelfand E W , Pabst R 
Published: July 2005

SummaryHistological data show perivascular recruitment of inflammatory cells in lung inflammation. However, the process of perivascular inflammation is yet-to-be characterized in any systematic manner at cell and molecular levels. Therefore, we investigated impact of genetic background on perivascular inflammation in acute or chronic airway inflammation in different strains of mice. Further, to address molecular mechanisms of perivascular inflammation, we examined immunohistochemical expression of vascular adhesion protein-1 (VAP-1) in chronic airway inflammation. Histological scoring revealed time and strain specific differences in perivascular recruitment of inflammatory cells in chronic and acute airway inflammation (P &lt; 0·05). The data show that A/J strain is significantly more susceptible for perivascular inflammation followed by BALB/c and C57BL/6, while C3H/HeJ strain showed no perivascular accumulation of inflammatory cells. Of the two strains examined for perivascular inflammation in acute airway inflammation, BALB/c showed more accumulation of inflammatory cells compared to C57BL/c. VAP-1 expression occurred in the endothelium of pulmonary arteries but not in alveolar septa or airways in the control as well as challenged mice. In the inflamed lungs from A/J mice, the VAP-1 staining in pulmonary arteries was more intense compared to the other strains. VAP-1 staining was generally observed throughout the pulmonary arterial wall in chronic lung inflammation. These data show that periarterial inflammation is influenced by the genetic background, and may be partially regulated by VAP-1.
Oligoclonal T cells are infiltrating the brains of children with AIDS: sequence analysis reveals high proportions of identical β-chain T-cell receptor transcripts
Authors: Lin W L , Fincke J E , Sharer L R , Monos D S , Lu S , Gaughan J , Platsoucas C D , Oleszak E L 
Published: July 2005

SummaryWe have recently described the presence of perivascular CD3+ CD45RO+ T cells infiltrating the brains of children with AIDS. To determine whether these infiltrates contain oligoclonal populations of T cells, we amplified by PCR β-chain T-cell receptor (TCR) transcripts from autopsy brains of four paediatric patients with AIDS. The amplified transcripts were cloned and sequenced. Sequence analysis of the β-chain TCR transcripts from all four patients revealed multiple identical copies of TCR β-chain transcripts, suggesting the presence of oligoclonal populations of T-cells. These TCR transcripts were novel. The presence of oligoclonal populations of T cells in the brains of these four paediatric patients with AIDS suggests that these T cells have undergone antigen-driven proliferation and clonal expansion very likely in situ, in the brains of these AIDS patients, in response to viral or self-antigens. Although the specificity of the clonally expanded β-chain TCR transcripts remains to be elucidated, none of the β-chain TCR transcripts identified in this study were identical to those specific for HIV-1 antigens that are currently reported in the GENBANK/EMBL databases. Certain common CDR3 motifs were observed in brain-infiltrating T cells within and between certain patients. Large proportions (24 of 61; 39%) of β-chain TCR clones from one patient (NP95-73) and 2 of 27 (7%) of another patient (NP95-184-O) exhibited substantial CDR3 homology to myelin basic protein (MBP)-specific TCR derived from normal donors or TCR expressed in the brain of patients with multiple sclerosis (MS) or with viral encephalitis. These two patients (NP95-73 and NP95-184-O) also shared HLA class II with the normal donors and the MS patients who expressed these homologous TCR. Pathologic examination at autopsy of the brains revealed the presence of myelin pallor only in patient NP95-73. T-cell clones identified in the brain of patients NP95-73 and NP95-184-O may recognize MBP or another CNS self antigen and this recognition may be restricted by either DRB1*15 or DQB1*0602 specificities.
High levels of glucocorticoid receptors in patients with active Crohn's disease may predict steroid resistance
Authors: Towers R , Naftali T , Gabay G , Carlebach M , Klein A , Novis B 
Published: July 2005

SummaryUp to 20% of Crohn's disease (CD) patients respond poorly to glucocorticoids (GC). A product of an alternative splicing of the glucocorticoid receptor (GR) premRNA, GRβ, may play a role as a dominant inhibitor of the glucocorticoid response. Increasing evidence suggests that inflammatory cytokines such as interleukin (IL)-18 alternate the splicing of the primary transcript between the two isoforms GRβ and GRα in hGR gene of CD patients. The aim of this study is to assess the expression of GRα and GRβ in patients with CD and to look for a possible correlation between these receptors and the response to glucocorticoid treatment. Forty-two CD patients and 17 healthy volunteers were studied. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed using real-time PCR techniques. Serum IL-18 protein levels were measured by enzyme-linked immunosorbent assay (ELISA). The amount of hGRα-mRNA in patients in remission was significantly lower than in controls (P &lt; 0·05). The amount of hGRβ-mRNA was significantly higher in GC-resistant patients in the active stage of disease compared with all other groups (P &lt; 0·05). Patients in the active stage of the disease had higher levels of IL-18 than patients in remission and both had higher levels than controls (P &lt; 0·05). The amounts of IL-18 were directly correlated with the amount of hGRβ mRNA in GC-resistant patients with an active disease. High levels of hGRβ might be connected to GC resistance. IL-18 might participate in the alternative splicing of the hGR preliminary mRNA of CD patients. The results support the theory that augmented hGRβ mRNA expression level in PBMC is connected with GC-resistance of CD patients.
Modulation of the immune response in pristane-induced lupus by expression of activation and inhibitory Fc receptors
Authors: Clynes Raphael , Calvani Nicola , Croker Byron P , Richards Hanno B 
Published: July 2005

SummaryAltered homeostasis in Fcγ receptor (FcγR) expression has been implicated in the induction of both immune complex-mediated glomerulonephritis and autoantibody production in systemic lupus erythematosus. FcγRI and III are required for immune complexes to activate inflammatory cells, thereby inciting tissue injury. In contrast, FcγRIIB functions as a negative regulator of immune complex-mediated inflammation and autoantibody production. We investigated the role of FcγRI/III versus FcγRIIB on pristane-induced lupus in mice. FcγRI/III and FcγRIIB-deficient (–/–) and control (+/+) BALB/c mice were injected with either pristane or PBS. Proteinuria and glomerular immune deposits were evaluated 9 months after treatment and serial sera were analysed for total IgG levels and lupus-specific autoantibodies. The incidence of nephritis was higher in pristane-treated FcγRIIB–/– mice than pristane-treated FcγRI/III–/– and +/+ mice. Hypergammaglobulinaemia and spontaneous anti-DNA/chromatin autoantibody production were associated with interleukin (IL)-6 over-expression in FcγRIIB–/– mice and were augmented further by pristane treatment when compared to both FcγRI/III–/– and +/+ mice. Lack of either FcγRIIB or FcγRI/III had little effect on both anti-nRNP/Sm and anti-Su production induced by pristane. Our results confirm that spontaneous autoimmunity occurs in the absence of FcγRIIB. Moreover, the lupus-like syndrome induced by pristane in BALB/c mice was regulated by opposing activating and inhibitory FcγRs. Activating FcγRs were required for significant proteinuria and unbridled activation in the absence of FcγRIIB dramatically exacerbated glomerular inflammatory responses. FcγRIIB may be a key modulator that suppresses cell activation in the inflammatory immune response in systemic lupus erythematosus in humans.
Bacterial lipopolysaccharide both renders resistant mice susceptible to mercury-induced autoimmunity and exacerbates such autoimmunity in susceptible mice
Authors: Abedi-Valugerdi M , Nilsson C , Zargari A , Gharibdoost F , DePierre J W , Hassan M 
Published: July 2005

SummaryThe initiation and severity of systemic autoimmune diseases are influenced by a variety of genetic and environmental factors, in particular bacterial infections and products. Here, we have employed bacterial lipopolysaccharide (LPS), which non-specifically activates the immune system, to explore the involvement of innate immunity in mercury-induced autoimmunity in mice. Following treatment of mouse strains resistant [DBA/2 (H-2d)] or susceptible [SJL(H-2s)] to such autoimmunity with mercuric chloride and/or LPS or with physiological saline alone (control), their immune/autoimmune responses were monitored. Resistant DBA/2 mice were rendered susceptible to mercury-induced autoimmunity by co-administration of LPS, exhibiting pronounced increases in the synthesis of IgG1 and IgE, high titres of IgG1 deposits in the kidneys and elevated circulating levels of IgG1 antibodies of different specificities. Furthermore, the percentages of the T cells isolated from the spleens of DBA/2 mice exposed to both mercury and LPS that produced pro-inflammatory cytokines were markedly increased by in vitro stimulation with phorbol myristate acetate (PMA) and ionomycin, which was not the case for splenic T cells isolated from mice receiving mercuric chloride, LPS or saline alone. In addition, exposure of susceptible SJL mice to mercury in combination with LPS aggravated the characteristic features of mercury-induced autoimmunity, including increased synthesis of IgG1 and IgE, the production of IgG1 anti-nucleolar antibodies (ANolA) and the formation of renal deposits of IgG1. In summary, our findings indicate that activation of the innate immune system plays a key role in both the induction and severity of chemically induced autoimmunity.
Accumulation of plasma cells expressing CXCR3 in the synovial sublining regions of early rheumatoid arthritis in association with production of Mig/CXCL9 by synovial fibroblasts
Authors: Tsubaki T , Takegawa S , Hanamoto H , Arita N , Kamogawa J , Yamamoto H , Takubo N , Nakata S , Yamada K , Yamamoto S , Yoshie O , Nose M 
Published: July 2005

Summary
Accumulation of plasma cells in the synovium is one of the diagnostic hallmarks in the histopathological manifestations of rheumatoid arthritis (RA). This seems to be prominent even prior to significant B cell infiltration and/or formation of lymphoid follicles in the synovium. To clarify the mechanism of early plasma cell accumulation, we examined in situ expression of chemokines and their receptors using synovial targeting biopsy specimens, which were obtained under arthroscopy from early RA patients. By immunohistochemical staining, plasma cells were found to express a chemokine receptor CXCR3, while synovial fibroblasts in the synovial sublining regions expressed its ligand, Mig/CXCL9. By reverse transcription-polymerase chain reaction (RT-PCR), using targeted lesions of synovial tissues obtained by laser capture microdissection, expression levels of Mig/CXCL9 in the synovial sublining regions were remarkably high and were likely to be associated with interferon (IFN)-γ expression. Furthermore, cultured synovial fibroblasts were confirmed to produce Mig/CXCL9 upon stimulation with IFN-γ. Our results indicate that in the early stage of RA, plasma cells expressing CXCR3 may be recruited directly from the circulation into the synovial sublining regions by its ligand, Mig/CXCL9, produced by synovial fibroblasts.
A human oral keratinocyte cell line responds to human heat shock protein 60 through activation of ERK1/2 MAP kinases and up- regulation of IL-1β
Authors: Pleguezuelos O , Dainty S J , Kapas S , Taylor J J 
Published: July 2005

SummaryHeat shock proteins (HSP) are released by cells in response to stress signals. It is hypothesized that pathogenic bacteria stimulate the cells in the periodontium to up-regulate the expression of HSP60, which would stimulate macrophages, and possibly other cells, to produce proinflammatory cytokines. We sought to determine whether oral keratinocytes responded to recombinant human HSP60 and to identify the signalling pathways involved. In addition, whether oral keratinocytes are a source of endogenous HSP60 was also investigated. RT-PCR revealed that rhHSP60 induced expression of the IL-1β gene in the Human Oral Keratinocyte (HOK-16B) cell line and it was highest at the lowest concentration used (0·1 µg/ml). These responses were mediated via activation of p44/42 MAP-kinases and to a lesser extend the MAP-kinase SAP/JNK. Similar data was obtained from analysis of intracellular signalling pathways in HOK-16B cells by rhHSP70 and LPS (from both E. coli and the oral pathogen Porphyromonas gingivalis). However, there was little activation of p38 by rhHSP60. Blocking of the p44/42 pathway decreased HSP60-induced IL-1β gene expression and protein secretion. In addition, we discovered that self-HSP60 proteins were constitutively secreted by HOK-16B cells. Secretion of self-HSP60 was up-regulated in cells treated with LPS from P. gingivalis, but down-regulated with LPS from E. coli. To summarize, oral keratinocytes respond to exogenous HSP60 by triggering expression of the inflammatory cytokine IL-1β through activation of p44/42 MAP kinase. Oral keratinocytes are also a source for self-HSP60 and the secretion of this protein may be differentially modified by LPS from different bacterial species. These results highlight the importance of oral keratinocytes and HSPs in the development of an immune response against bacterial infection.
Differential early mitogen‐activated protein kinase activation in hyperglycemic ischemic brain injury in the rat
Authors: Farrokhnia N. , Roos M. W. , Terént A. , Lennmyr F. 
Published: July 2005

AbstractBackground  Hyperglycemia aggravates brain injury induced by focal ischemia‐reperfusion. The mitogen‐activated protein kinase (MAPK) members extracellular‐signal regulated kinase (Erk) and c‐Jun N‐terminal kinase (JNK) have been proposed as mediators of ischemic brain injury, and Erk is strongly activated by combined hyperglycemia and transient global ischemia. It is unclear whether similar MAPK activation appears in focal brain ischemia with concomitant hyperglycemia.Design  Hyperglycemia was induced in rats by an intraperitoneal bolus of glucose (2 g kg−1). The rats were then subjected to 90 min of transient middle cerebral artery occlusion (MCAO). Erk and JNK activation were investigated with immunofluorescence and Western blot along with infarct size measurement based on tetrazolium staining and neurological score.Results  The hyperglycemic rats showed increased tissue damage and impaired neurological performance after 1 day compared with controls. The hyperglycemia was generally moderate (< 15 mM). Erk activation was increased after 30 min of reperfusion in the ischemic cortex of the hyperglycemic rats, while JNK activation was present on the contralateral side. Phospho‐Erk immunofluorescence revealed marked neuronal activation of Erk in the ischemic cortex of hyperglycemic rats compared with controls.Conclusion  Besides confirming the detrimental effects of hyperglycemia on focal ischemia‐reperfusion, this study shows that hyperglycemia strongly activates the pathogenic mediator Erk in the ischemic brain in the early phase of reperfusion. JNK activation at this stage is present in the nonischemic hemisphere. The functional relevance of these findings needs further investigation.
News in gut‐brain communication: a role of peptide YY (PYY) in human obesity and following bariatric surgery?
Authors: Hanusch‐Enserer U. , Roden M. 
Published: July 2005

AbstractRecent advances in obesity research focused on neuroendocrine control of food intake, appetite and body weight balance. Gut hormones, which are sequentially released from different regions of the gut, send signals to the areas of appetite control in the central nervous system causing a release of counter‐regulatory hormones also originating from the gastrointestinal system. Ghrelin, a peptide secreted from the gastric fundus is released just before meal intake and stimulates hunger and food intake. Recently, peptide YY has been suggested to counteract ghrelin by inducing satiety and reducing appetite and caloric intake. While the effects of PYY on various gastrointestinal functions are well described, its action on weight loss is less known. Controversial results on the effect of exogenous administration of PYY3–36 opened the discussion on the respective roles of PYY and/or PYY3–36 in body weight homeostasis in man.
Angiotensin converting enzyme gene, smoking and mortality in a population‐based study
Authors: Arias‐Vásquez A. , Sayed‐Tabatabaei F. A. , Schut A. F. C. , Hofman A. , Bertolli‐Avella A. M. , Vergeer J. M. , Aulchenko Y. S. , Witteman J. C. M. , Van Duijn C. M. 
Published: July 2005

AbstractBackground  The genetic and environmental risk factors, which may influence longevity and mortality, have received much attention during more than one decade. One of the major risks for mortality is cardiovascular disease and the renin angiotensin system (RAS) plays a major role in maintaining blood pressure homeostasis. In this system, the Angiotensin Converting Enzyme (ACE) is one of the key regulators and has been studied in relation to cardiovascular disease and mortality. We aimed to evaluate if the ACE I/D polymorphism is related to total mortality in the elderly.Materials and methods  Some 6968 elderly individuals from the Rotterdam study were genotyped for this polymorphism. Smoking was studied as a possible covariable or effect modifier. To examine the effect of the ACE genotype on mortality, a Cox proportional hazards model was fitted.Results  Our results show an increased risk of total mortality in subjects with age at death below 65 years carriers of the DD genotype (HR 1·8, 95% CI 1·1–2·9, P = 0·016). This association was significant in total and cause specific mortality only in those who smoke (P‐value < 0·001 for gene–age interaction). Our findings suggest that the ACE gene is rather associated with early mortality than with late.Conclusions  Individuals who carry the DD genotype appear to be susceptible to early mortality if they smoke, suggesting a possible interaction between smoking and the ACE gene.
PCR for Detection of Mycobacterium tuberculosis in Experimentally Infected Dogs
Authors: Bonovska M. , Tzvetkov Y. , Najdenski H. , Bachvarova Y. 
Published: July 2005

SummaryThe susceptibility of dogs to infection with Mycobacterium tuberculosis was studied through different ways of experimental infection. The examination shows, that in most cases the disease runs subclinically with pathological changes localized mainly in the lungs, lymph nodes, small intestines, liver, kidneys and spleen. Histological findings demonstrate granulomatous inflammation with caseosation and predominance of epitheloide macrophages and single lymphocytes. Tissue samples from internal organs of experimentally infected dogs as well as non‐infected but contact animals were investigated by direct PCR. Specific PCR‐products were obtained in 44 of 96 studied samples. Eighty‐three (86.5%) of PCR results coincided with bacteriological finds, 82 (85.4%) with the pathological and 71 (74.0%) simultaneously with bacteriological and pathological results. The observed specific DNA products in tissue samples of infected and non‐infected dogs demonstrate significant sensitivity of PCR method. It could be assumed that the transmission of M. tuberculosis infection is possible by close contact between ill and healthy dogs and that the naturally infected dogs or dogs suffering from tuberculosis may serve as a permanent source of infection to humans and other animals.