bluuebunny/crossref_metadata_2025_split huggingface dataset:
Triamcinolone acetonide modulates permeability and intercellular adhesion molecule-1 (ICAM-1) expression of the ECV304 cell line: implications for macular degeneration
Authors: Penfold P L , Wen L , Madigan M C , Gillies M C , King N J C , Provis J M 
Published: March 2003

SUMMARYWhilst animal studies and a pilot clinical trial suggest that intravitreal triamcinolone acetonide (TA) may be useful in the treatment of age-related macular degeneration (AMD), its mode of action remains to be fully elucidated. The present study has investigated the capacity of TA to modulate the expression of adhesion molecules and permeability using a human epithelial cell line (ECV304) as a model of the outer blood–retinal barrier (BRB). The influence of TA on the expression of ICAM-1 and MHC-I was studied on resting and phorbol myristate acetate (PMA)- or interferon-gamma (IFN-γ)- and/or tumour necrosis factor-alpha (TNF-α)-activated cells using flow cytometry and immunocytochemistry. Additionally, ECV304 cells were grown to confluence in uncoated Transwell chambers; transepithelial resistance (TER) across resting and PMA-activated cells was monitored. TA significantly decreased the paracellular permeability of ECV304 cells and down-regulated ICAM-1 expression, consistent with immunocytochemical observations. PMA-induced permeability changes were dose-dependent and TA decreased permeability of both resting and PMA-activated monolayers. MHC-I expression by ECV304 cells however, was not significantly affected by TA treatment. The modulation of TER and ICAM-1 expression in vitro correlate with clinical observations, suggesting re-establishment of the BRB and down-regulation of inflammatory markers are the principal effects of intravitreal TA in vivo. The results further indicate that TA has the potential to influence cellular permeability, including the barrier function of the retinal pigment epithelium (RPE) in AMD-affected retinae.
CD14+CD16+ monocyte subpopulation in Kawasaki disease
Authors: Katayama K , Matsubara T , Fujiwara M , Koga M , Furukawa S 
Published: March 2003

SUMMARY
Kawasaki disease (KD) is an acute febrile illness caused by vasculitis, occurring in early childhood. We have demonstrated that the activation of monocytes/macrophages plays a central role during acute KD. Recently, it has been reported that the CD14+CD16+ monocyte subpopulation plays a more important role in inflammation. In this study, we investigated the peripheral blood CD14+CD16+ monocyte subpopulation by flow cytometry, and serum levels of IL-10 and IL-12 using a sandwich ELISA in 28 KD patients. We also investigated this subpopulation in patients with bacterial infections, mononucleosis and anaphylactoid purpura, since the cause of KD remains unknown. We observed an increase in the number of CD14+CD16+ monocytes with acute KD, which was a positive correlation with C-reactive protein levels, and we observed only the patients with severe bacterial infections had increased this subpopulation during the acute stage among control diseases. In addition, we found that the serum levels of IL-10, but not IL-12, were higher during acute KD. These data suggest that increased peripheral blood CD14+CD16+ monocytes are part of the regulatory system of monocyte function during acute KD.
Tumour necrosis factor-alpha (TNF-α) enhances lymphocyte migration into rheumatoid synovial tissue transplanted into severe combined immunodeficient (SCID) mice
Authors: Wahid S , Blades M C , De Lord D , Brown I , Blake G , Yanni G , Haskard D O , Panayi G S , Pitzalis C 
Published: March 2003

SUMMARYAdhesion mechanisms play a major role in the recruitment of peripheral blood lymphocytes (PBL) which characteristically infiltrate rheumatoid arthritis (RA) synovium and other chronically inflamed tissues. Through a sequential series of complex integrated adhesion and signalling events, ‘multistep model of migration’, specific subsets of PBL are recruited into inflamed tissues. In this process both leucocyte receptors and microvascular endothelial (MVE) counter-receptors play a critical role. The MVE in particular, during an inflammatory state, is the target of various inflammatory mediators that cause the up-regulation of several cell adhesion molecules (CAM). One of the most important factors known to be a powerful inducer of MVE CAM is TNF-α. Conversely, blocking TNF-α causes a down-modulation of CAM expression. To test directly the capacity of TNF-α to induce cell migration into RA synovium we adapted a model in which synovial grafts were implanted into SCID mice subcutaneously. Using this model we demonstrate that: (i) transplants remain viable and become vascularized and fed by mouse subdermal vessels; (ii) the mouse vasculature connects to the transplant vasculature which maintains the ability to express human CAM; (iii) intragraft injections of TNF-α up-regulate the expression of human CAM, following the down-regulation which occurred 4 weeks post-transplantation; and (iv) the up-regulation of graft CAM is associated with increased human PBL migration into the transplants. This study provides direct evidence in vivo of the capacity of TNF-α to induce cell migration. In addition, it provides the experimental background for the optimal use of this model.
Glycosylphosphatidylinositol (GPI)-deficient Jurkat T cells as a model to study functions of GPI-anchored proteins
Authors: Bastisch I , Tiede A , Deckert M , Ziolek A , Schmidt R E , Schubert J 
Published: March 2003

SUMMARYMany cell surface proteins attached to the membrane by GPI are involved in cell signalling. However, the role of the GPI membrane anchor itself remains poorly understood. GPI-defective cells from patients with paroxysmal nocturnal haemoglobinuria (PNH) are relatively resistant to apoptosis induction. We developed a Jurkat T cell model for GPI deficiency by isolating a GPI-negative mutant, which is defective in the GPI biosynthetic gene PIG-A. Using retroviral PIG-A gene transfer along with the transfer of a vector control, we obtained two genetically identical cell lines, distinguished only by expression of the PIG-A gene and, thus, their ability to produce GPI. Cell proliferation and survival were not affected by this difference. Apoptotic stimuli such as serum starvation and camptothecin exposure elicited similar responses. In contrast, GPI-defective Jurkat cells were more susceptible to Fas-mediated apoptosis than GPI-positive cells. These results indicate that a deficiency in GPI-anchored proteins, as is found in PNH, does not confer resistance to apoptosis.
Serum interferon-gamma-inducing factor/IL-18 levels in primary biliary cirrhosis
Authors: Yamano T , Higashi T , Nouso K , Nakatsukasa H , Kariyama K , Yumoto E , Kobayashi Y , Yamamoto K , Iwagaki H , Yagi T , Tanimoto T , Kurimoto M , Tanaka N , Tsuji T 
Published: March 2003

SUMMARYPrimary biliary cirrhosis is an autoimmune disease of the liver in which T helper 1 cytokines predominate over those of T helper 2 in the pathogenesis. Interleukin-18 (IL-18), for which the gene was recently cloned, is a novel T helper 1 cytokine, which augments interferon-gamma production. We designed this study to clarify the role of IL-18 in primary biliary cirrhosis and to examine whether serum IL-18 level can be a prognostic indicator for the disease. Serum IL-18 levels were measured using an enzyme linked immuno sorbent assay with mouse monoclonal antibodies. Twenty-two healthy volunteers, 31 patients with primary biliary cirrhosis (Scheuer's stage I, 13; II, 10; and IV, 8), 20 patients with autoimmune hepatitis, 11 patients with virus-related liver cirrhosis and six patients with obstructive jaundice were enrolled. Significant differences of serum IL-18 levels were observed between patients with Scheuer's stage IV and those with stage I, or II, virus-related liver cirrhosis and obstructive jaundice (P &lt; 0·05). The IL-18 levels in primary biliary cirrhosis increased according to the disease progression, and fell promptly after living-related liver transplantation. Moreover, serum IL-18 levels in primary biliary cirrhosis were correlated with serum bilirubin concentrations and the Risk scores of the Mayo Clinic prognostic model for the disease. The IL-18 levels observed in patients with autoimmune hepatitis were also elevated, and correlated with the activity of the disease. These results indicate that serum interleukin-18 levels reflect the severity of primary biliary cirrhosis, the activity of autoimmune hepatitis, and may be an additive prognostic indicator in primary biliary cirrhosis.
Increased transforming growth factor-beta (TGF-β)-secreting T cells and IgA anti-cardiolipin antibody levels during acute stage of childhood Henoch–Schönlein purpura
Authors: Yang Y-H , Huang M-T , Lin S-C , Lin Y-T , Tsai M-J , Chiang B-L 
Published: March 2003

SUMMARY
Henoch–Schönlein purpura (HSP) is a small vessel vasculitis characterized by increased serum IgA and IgA-dominant immune complex deposition in lesions. The involvement of IgA implies a probable role for TGF-β, a major factor in IgA production, in the pathogenesis of HSP. Among IgA antibodies, serum IgA anti-cardiolipin antibodies (aCL) have been found in many diseases, including vasculitis. In addition to the clinical presentations and laboratory parameters, we further investigated the roles of IgA aCL and TGF-β in childhood HSP. Twenty-six Chinese children with the diagnosis of HSP were enrolled. Blood samples from these patients were collected at both acute and convalescent stages. Intracellular staining of lymphocytes was performed to enumerate type 1 (interferon-gamma-secreting), type 2 (IL-4-secreting), and type 3 (TGF-β-secreting) helper T cells. Serum levels of TGF-β were detected by ELISA. Serum IgA aCL of 21 of 26 patients at the acute stage, 11 of them at the convalescent stage, were measured by ELISA. The data showed that IgA aCL serum levels were significantly elevated in patients compared with healthy controls (P &lt; 0·001), and those patients at the convalescent stage (P &lt; 0·001). In addition, TGF-β-secreting T cells were significantly elevated during the acute stage, and decreased at the convalescent stage. Although more studies are needed, the high prevalence of IgA aCL and increased TGF-β-secreting T cells in children with acute HSP revealed some points which should permit a better understanding of the pathogenesis of HSP.
Role of IL-10 in invasive aspergillosis: increased resistance of IL-10 gene knockout mice to lethal systemic aspergillosis
Authors: Clemons K V , Grunig G , Sobel R A , Mirels L F , Rennick D M , Stevens D A 
Published: March 2003

SUMMARYIL-10 is associated with a Th2 response, down-regulation of a Th1 response and macrophage activation. We assessed the role of IL-10 during systemic infection with Aspergillus fumigatus. Systemic aspergillosis was established in female C56Bl/6 IL-10−/– (KO) and wild-type (WT) C57Bl/6 mice by i.v. administration of 1 × 105−6 × 105 conidia of A. fumigatus. In two experiments, KO survived longer than did WT (P &lt; 0·001). Determination of fungal burdens in the kidneys and brain showed that KO carried significantly lower burdens in both organs than did WT on day 3 (P &lt; 0·001). Semiquantitative histological analyses showed fewer inflammatory foci/mm2 in brain and kidneys of KO than WT (P &lt; 0·03 and &lt; 0·001, respectively) and that extent of infection and associated tissue injury were greater in WT. Although beneficial in some bacterial infections, exogenous IL-10 has been shown deleterious in models of fungal infection. Our data indicate IL-10 is deleterious during systemic aspergillosis infection, increasing the host susceptibility to lethal infection. We speculate this might be related to greater Th2 or lesser Th1 responses, or down-regulation of macrophage responses, in WT compared with KO.
IL-10 stimulates production of platelet-activating factor by monocytes of patients with active systemic lupus erythematosus (SLE)
Authors: Bussolati B , Rollino C , Mariano F , Quarello F , Camussi G 
Published: March 2003

SUMMARYIL-10 displays modulatory properties on the synthesis of platelet-activating factor (PAF), a potent inflammatory mediator of vascular injury. Despite the fact that IL-10 is considered to be an anti-inflammatory cytokine, IL-10 levels correlate with disease activity in SLE. Moreover, in SLE IL-10 is unable to exert its immunosuppressive and anti-inflammatory effects. We have investigated the ability of IL-10 to stimulate PAF production from monocytes of SLE patients. Spontaneous and IL-10-stimulated PAF production by peripheral blood monocytes was measured in active (n = 13) and inactive (n = 14) SLE patients and in 15 normal control subjects. We observed that monocytes derived from patients with active SLE, but not from controls or inactive SLE, spontaneously produced significant amounts of PAF. Moreover, IL-10 enhanced the synthesis of PAF from monocytes of active SLE patients only. IL-10-induced PAF production correlated with the severity of the disease and with the extent of proteinuria. These results indicate that IL-10 only stimulates the synthesis of PAF from monocytes of SLE patients when immunologically active, suggesting that IL-10 may possess a paradoxical proinflammatory effect in SLE by promoting the production of PAF, a secondary mediator of inflammation.
Hepatitis C virus (HCV) in lymphocyte subsets and in B lymphocytes expressing rheumatoid factor cross-reacting idiotype in type II mixed cryoglobulinaemia
Authors: Fornasieri A , Bernasconi P , Ribero M L , Sinico R A , Fasola M , Zhou J , Portera G , Tagger A , Gibelli A , D’Amico G 
Published: March 2003

SUMMARYThe IgMk rheumatoid factors (RF) of type II mixed cryoglobulinaemia (MC) react, in 95% of cases, with MoAbs against the cross-reactive idiotypes (CRI) Cc1 or Lc1 (corresponding to the products of the VH1 and VH4 genes). MC is closely associated with HCV infection, a virus which infects lymphocytes and may replicate in B cells. It has been suggested that HCV may induce clonal selection of B cells producing monoclonal IgMk RF in type II MC. To verify whether HCV is enriched in B cells, and in the subsets expressing Cc1 and Lc1 CRI, we studied peripheral blood lymphocytes from eight patients with MC and HCV RNA-positive sera. Seven patients had RF reacting with anti-Cc1, the other with anti-Lc1 CRI. Total lymphocytes, T cells, B cells, and Cc1+ or Lc1+, Cc1− or Lc1− B cells were purified using MoAb-coated magnetic beads. Lymphocyte subsets were then diluted to give a range of 1 × 106−1 × 103 cells and tested for HCV RNA by reverse transcriptase-polymerase chain reaction. HCV was found exclusively in B cells in seven out of eight patients. In three patients HCV was enriched in the Cc1+ cells. In one of these patients, HCV was found exclusively in Cc1+ cells, with Cc1− cells being HCV−. The data indicate that B cells from type II MC patients are almost constantly infected by HCV. In selected cases, B cell subsets expressing IgMk RF CRI are the prevalent cell type infected by HCV. Our data suggest HCV involvement in B cell dysregulation leading to cryoprecipitable IgMk RF production.
Neutrophil accumulation induced by bacterial lipopolysaccharide: effects of dexamethasone and annexin 1
Authors: Allcock G H , Allegra M , Flower R J , Perretti M 
Published: March 2003

SUMMARYAnnexin 1 (ANX-1) can reduce leucocyte migration in response to cytokines and chemokines in some rodent models of inflammation. However, its effectiveness against an inflammatory stimulus as strong as bacterial lipopolysaccharide (LPS) is unknown. Thus, we have examined whether ANX-1 can modulate LPS-induced neutrophil accumulation in the rat, as assessed by intravital microscopy and by myeloperoxidase (MPO) assay. The anti-inflammatory glucocorticoid, dexamethasone (DEX) was also studied for comparison. LPS superfusion induced adhesion of leucocytes to the endothelium and a subsequent increase in emigration from rat post-capillary venules over 2 h as assessed by intravital microscopy. Either ANX-1 or DEX was able to attenuate this adhesion and emigration of leucocytes. MPO activity in the lung, kidney and ileum was elevated after a 6-h exposure to LPS (intraperitoneal), indicating accumulation of neutrophils in these tissues. DEX attenuated the LPS-induced increase in MPO in the ileum but had no effect on MPO in the lungs or kidneys. This would suggest that the underlying mechanism by which neutrophils accumulate in the ileum, and more generally in the gastrointestinal compartment, is different from other vascular beds. ANX-1 had no effect on the LPS-induced increase in MPO activity in any of the tissues studied. Thus, from these data, ANX-1 appears to reduce leucocyte adhesion and emigration induced by a short-term (2 h), but not a longer (6 h) exposure to LPS.
Expression of IL-18 byMycobacterium avium-infected human monocytes; association withM. aviumvirulence
Authors: Shiratsuchi H , Ellner J J 
Published: March 2003

SUMMARYDisseminated Mycobacterium avium infection is the most frequent bacterial infection in patients with advanced AIDS and also associated with interferon-gamma (IFN-γ) or IL-12 receptor deficiency. IFN-γ is a key cytokine in host defence against M. avium infection. Expression of IL-18, a potent IFN-γ inducer, and IFN-γ by human monocytes after infection with M. avium was examined. Monocytes were co-cultured with isogenic smooth-transparent (SmT: virulent) or smooth-domed (SmD: avirulent) M. avium strains (10 organisms per monocyte). Infection with the SmD strain induced significantly higher concentration of IL-18 and IFN-γ in culture supernatants than did the SmT strain. IFN-γ production in response to M. avium was partially inhibited by anti-human IL-18 MoAb. Both recombinant human IL-12 (77 ± 42 pg/ml, control versus 1492 ± 141 pg/ml, cultures with IL-12 1 ng/ml) and IL-18 (126 ± 37 pg/ml, control versus 2683 ± 864 pg/ml, cultures with IL-18 10 ng/ml) augmented M. avium-induced IFN-γ production. Freshly isolated uninfected monocytes expressed constitutive levels of IL-18. Following infection with M. avium, enhancement of IL-18 mRNA expression peaked at 3–6 h. IL-18 protein was detected in monocyte lysates as early as 1 h after infection with both SmT and SmD M. avium strains by Western blotting. Higher IL-18 expression by monocytes infected with the avirulent strain may result in more IFN-γ production, thus modulating its pathogenicity. Local induction of IL-18 may be important both for M. avium pathogenicity and host defence and become a potential candidate for immunotherapy.
Reduced systemic IgG levels against peptidoglycan in rheumatoid arthritis (RA) patients
Authors: Schrijver I A , De Man Y A , Melief M -J , Van Laar J M , Markusse H M , Klasen I S , Hazenberg M P , Laman J D 
Published: March 2003

SUMMARY
The gut flora is believed to play a role in the pathogenesis of RA. Peptidoglycan, a major cell wall component of Gram-positive bacteria, is a candidate antigen because of its capability to trigger production of proinflammatory cytokines, to induce arthritis in rodents, and because of its presence in antigen-presenting cells in RA joints. We investigated whether the systemic and local antibody levels against a peptidoglycan–polysaccharide (PG–PS) are related to the presence and disease activity of RA. Significantly lower levels of systemic IgG directed against PG–PS were found in healthy females compared with healthy males, and systemic IgA levels specific for PG–PS were negatively correlated with age. Levels of systemic IgG directed against PG–PS were significantly reduced in RA patients compared with sex- and age-matched healthy controls. Local (synovial fluid) levels of IgG did not correlate with disease activity whereas synovial fluid levels of IgA correlated positively with disease activity. These data suggest that IgG in healthy people mediates protection against spreading of PG to non-mucosal sites.
Elevated IL-5 levels in pleural fluid of patients with paragonimiasis westermani
Authors: Taniguchi H , Mukae H , Matsumoto N , Tokojima M , Katoh S , Matsukura S , Ogawa K , Kohno S , Nawa Y 
Published: March 2003

SUMMARY
To investigate the pathogenic mechanisms of eosinophilic pleural effusion in patients with paragonimiasis, we measured the levels of IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-γ) in pleural effusions. Samples were obtained from 11 patients with Paragonimus westermani infection. In addition, samples from 12 patients with pleural transudates, 16 with tuberculous pleurisy, seven with empyema and 20 with lung cancer were also examined. Eosinophilia was remarkable in peripheral blood (range 4–34%, median 23·4%) and pleural fluid (range 0–95%, median 71%) of paragonimiasis patients. IL-5 concentrations in pleural effusions of paragonimiasis were markedly higher than those in other groups. Although marked elevation of GM-CSF and IFN-γ levels was observed in pleural effusion of empyema and tuberculosis patients, it was marginal in the pleural effusion of paragonimiasis patients. In paragonimiasis patients, IL-5 levels in the pleural effusion correlated well with the percentage of eosinophils in peripheral blood and pleural fluid. Such a correlation was not observed between GM-CSF levels in pleural effusion and percentages of eosinophils in pleural fluid or peripheral blood. Our findings suggest that in paragonimiasis IL-5 in the local inflammatory site is particularly important in mediating eosinophilia in peripheral blood and pleural effusion.
Up-regulation of prostaglandin E receptor EP2 and EP4 subtypes in rat synovial tissues with adjuvant arthritis
Authors: Kurihara Y , Endo H , Akahoshi T , Kondo H 
Published: March 2003

SUMMARY
To evaluate the role of the prostaglandin E receptor (EP) subtypes in the development of inflammatory synovitis, we examined EP subtype mRNA distribution in the synovial tissue of rats with adjuvant arthritis and the effect of selective EP agonists on cytokine production by cultured rat synovial cells. We used reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization to measure the level of EP subtype (EP1, EP2, EP3, and EP4) mRNA expression in synovial tissues and cultured synovial cells from the arthritic joints of rats. RT-PCR and ELISA were used to analyse the effects of two selective EP agonists on IL-6 production by cultured rat synovial cells. EP2 and EP4 mRNA expression in inflamed synovial tissues was up-regulated. EP2 and EP4 mRNA were co-expressed in synovial macrophages and fibroblasts in inflamed tissues. EP4 and EP2 agonists both inhibited IL-1-induced IL-6 production. Our results suggest that prostaglandin E2 regulates the functions of synovial macrophages and fibroblasts through EP2 and EP4, which are induced by inflammatory stimuli in rats with adjuvant arthritis.