Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of treatment with a monoclonal antibody (R73 mAb) against T cell receptor alpha/beta (TCR-alpha/beta) on both established adjuvant arthritis (EAA) and established collagen-induced arthritis (ECIA) in rats have been investigated. Rats were treated with R73 mAb when arthritis reached a peak. Treatment with the anti-TCR-alpha/beta mAb markedly suppressed EAA, whereas ECIA was not affected by the mAb treatment. Histologically, R73 mAb-treated rats with EAA showed mild hyperplasia of synovial tissues, sparse infiltration of inflammatory cells, and minimal erosion of cartilage, whereas arthritic rats treated with PBS and an irrelevant control mAb against Giardia had marked hyperplasia of synovium with pannus, massive inflammatory cell infiltrate, and severe destruction of cartilage and subchondral bone. R73 mAb-treated rats with ECIA exhibited pronounced formation of pannus containing many inflammatory cells and marked cartilage and subchondral damage similar to those in arthritic rats that received the control treatments. Treatment with R73 mAb depleted markedly alpha/beta+ T cells in both peripheral blood and synovial tissues of rats with EAA and ECIA. R73 mAb treatment was associated with marked reduction in arthritogen-specific delayed-type hypersensitivity responses in both EAA and ECIA. The titers of antibodies against type II collagen produced in rats with ECIA were not affected by the mAb. Thus, alpha/beta+ T cells appear to have a central role in EAA, but not in chronic ECIA.
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PMID:Depletion of alpha/beta T cells by a monoclonal antibody against the alpha/beta T cell receptor suppresses established adjuvant arthritis, but not established collagen-induced arthritis in rats. 137 48

In this report we are able to show that intravenous (i.v.) application (day 0) of a nonapeptide (residues 26-34) from the human C1q A-chain (designated peptide A-C1q) prior to intradermal (i.d.) administration of chicken type II collagen (CII) in arthritis-susceptible DBA/1 mice (H2q), leads to abrogation of polymorphonuclear neutrophil (PMN) invasion into the joints. This nonapeptide exhibits epitope characteristics and high homology to residues 137-147 of CB11 (a cyanogen bromide fragment of chicken CII, known to contain both arthritis inducing and suppressing determinants). Arthritis index was lowest in animals pretreated i.v. with CII (as internal control), though animals pretreated i.v. with peptide K (residues 137-147 with an additional glycine residue from CB11) or peptide A-C1q exhibited comparative arthritic indices. Only in the arthritis-positive control group (day 0: PBS i.v.) did i.d. application of CII lead to invasion of PMN into the synovial layer and the joint space. Analysis of antibody (Ab) responses at day 48 after i.v. immunization (day 0) and CII challenge (day 7) revealed IgE-Abs to native CII and also to native C1q. IgG titers to CII were highest in animals pretreated with peptide A-C1q. Abs from this group, exhibiting activity to peptide A-C1q (immunizing antigen), were of mainly IgG1 and IgG3 isotypes. Evaluation of the immune response following i.v. application of peptide A-C1q or CII, prior to i.d. CII administration, in DBA/1 mice, revealed IgM responses to peptide A-C1q and peptide K, but not to CII. Intravenous application of peptide A-C1q led to generation of IgG3-Abs reacting only with peptide A-C1q and peptide K, but not with native CII. Additionally, i.v. application of peptide A-C1q elicited IgG responses to a pentapeptide, resembling amino acid residues 26-30 (K-G-E-Q-G) of the C1q A-chain. This five residue antigenic determinant is present in peptide K, in chicken and human CII as well as in human C1q. No specific IgE response to any of the antigens tested could be detected. Since a peptide from the C1q A-chain is both capable of eliciting immune responses and modulating CII-induced arthritis in mice, we postulate that the collagen-like complement component C1q is involved in the development of CII-induced inflammatory arthritic lesions, and may represent, in vivo, the early antigen responsible for inducing anticollagen antibodies prior to CII in hyaline cartilage becoming available as antigen.
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PMID:Modulation of type II collagen-induced arthritis in DBA/1 mice by intravenous application of a peptide from the C1q-A chain. 139 37

In an attempt to examine the in vivo proinflammatory properties of IL-1, the effects of rIL-1 beta on the development of collagen-induced arthritis in mice were investigated. The results presented in this paper demonstrated that the administration of rIL-1 beta via mini-osmotic pumps into DBA/1 mice which were suboptimally immunized with native chick type II collagen (NcII) markedly accelerated the onset as well as the progression of the arthritic disease. When IL-1-containing osmotic pumps were s.c. implanted onto mice 18 days post-collagen immunization, clinical signs of arthritis appeared within 3 to 4 days after the implant with the pumps. Maximal incidence of arthritis which was usually 80 to 100% occurred between the 6th and 7th day after the administration of rIL-1 beta. Histologic analyses revealed that the knee and ankle joints from mice which were treated with rIL-1 beta for 7 days were most severely and consistently affected. Furthermore, these IL-1-treated mice exhibited granulocytic hyperplasia within the marrow as well as marked peripheral blood neutrophilia. By contrast, arthritis was not observed during the 7-day course of the IL-1 study in the following control groups: 1) mice that were only immunized with NcII, and 2) collagen-immunized mice which received osmotic pumps containing PBS. A substantial number of these collagen-immunized mice which were not treated with IL-1 eventually developed arthritis but at later times after the incidence of arthritis had peaked in the IL-1-treated group. In addition, unimmunized mice failed to develop arthritis upon treatments with IL-1 beta. Moreover, the humoral responses to NcII were not altered in the IL-1-treated mice. Thus, these in vivo studies suggest that IL-1 is potentially capable of triggering the various inflammatory events of collagen-induced arthritis, and thereby, contribute to the pathogenesis of murine arthritis.
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PMID:In vivo administration with IL-1 accelerates the development of collagen-induced arthritis in mice. 326 Sep 13

Collagen-induced arthritis (CIA) developed in 70 to 90% of rats immunized with heterologous type II collagen. CIA was reduced to 0 to 18% when rats were injected i.v., i.e., pretreated, with 1 mg of soluble native type II collagen before immunization. Concomitant with the suppression of CIA were significant suppression of IgM, IgG, and delayed-type hypersensitivity (DTH) responses to type II collagen. Suppression of CIA and immunity to collagen was antigen-specific, related to dose and route of administration, and occurred only when 1 mg of collagen was injected i.v. either 32, 7, or 4 days before, or 7 days after immunization. Once CIA was established, however, neither arthritis nor immunity could be suppressed. To determine if adjuvant-induced arthritis (AIA), like CIA, could be suppressed by i.v. pretreatment with type II collagen, rats were given 1 mg of type II collagen or PBS i.v. before injection with mycobacteria and oil. AIA was not suppressed, and arthritis appeared in both groups at a similar incidence and severity. Sera from 26 rats with severe AIA that was collected between days 14 and 35 after injection were assayed for IgG to homologous rat type II collagen and were found to be negative. These findings further support the hypothesis that CIA in rats is mediated by immunity to type II collagen and also suggest that CIA and AIA have different primary pathogenic mechanisms.
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PMID:Collagen-induced arthritis in rats: antigen-specific suppression of arthritis and immunity by intravenously injected native type II collagen. 619 9

The accumulation of LDL in the arterial intima is considered a key event in atherogenesis. We investigated the binding of oxidized LDL (ox-LDL) to microtiter plates coated with type I or II collagen, laminin, fibronectin, or poly-D-lysine. Oxidation of LDL, 125I-LDL, or Eu(3+)-LDL was performed with CuCl2, varying the time of oxidation. Bound lipoprotein was assessed by counting radioactivity or fluorescence in the wells. Binding of highly ox-LDL in PBS followed the order: type I collagen > poly-D-lysine > type II collagen > laminin > fibronectin. Comparing various collagen types, the binding of ox-LDL followed the order: type I > type V and, type III > type IV > type II collagen. Binding of ox-LDL in PBS was dependent on an increase in negative charge of ox-LDL. Testing certain amino acids as competitors for binding of highly ox-LDL to type I collagen put lysine first, followed by arginine and histidine. On laminin, histidine competed most, followed by lysine and arginine. When studying the influence of Na+, K+, Ca2+, Mg2+ (equivalent to their concentrations in the interstitial fluid), native LDL, moderately ox-LDL, and highly ox-LDL showed the same affinity to type I collagen. However, a fivefold dilution of the buffer increased the affinity of moderately and highly ox-LDL 3.9- and 10-fold compared with native LDL. Application of the F(ab')2 from a monoclonal antibody to ox-LDL revealed a strong competition of the binding of highly ox-LDL to type II collagen (60%), laminin (35%), type I collagen (20%), and poly-D-lysine (15%), whereas the binding to fibronectin was not affected.
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PMID:In vitro interactions of oxidatively modified LDL with type I, II, III, IV, and V collagen, laminin, fibronectin, and poly-D-lysine. 940 48

The present study was aimed at investigating whether the expression of Fas ligand (FasL) by CHO cells transfected with IL-4 (CHO/IL-4) or IL-10 (CHO/IL-10) genes would improve the effect of the cytokine. DBA/ 1 mice immunized with type II collagen were treated with suboptimal doses of transfected CHO cells (a single s. c. injection of 2 x 10(5) cells) around onset of arthritis. Severe collagen-induced arthritis (CIA) developed in the control groups injected with PBS, CHO /beta-galactosidase/FasL, CHO/IL-4 or CHO/IL-10 cells. In contrast, administration of CHO/IL-4/FasL, but not CHO/IL-10/FasL, cells significantly reduced the clinical severity and resulted in rapid and sustained suppressive effect. Amelioration of CIA was not due to a prolonged in vivo secretion of IL-4 since expression of FasL by CHO cells shortened the in vivo survival of the xenogeneic cells. In fact, administration of FasL(+) cells was associated with a decreased proportion of Mac1(+) neutrophils in the blood and an increased expression of myeloperoxidase at the site of engineered cell engraftment. These findings suggest that the mechanism underlying the beneficial effect of IL-4 delivered by cells expressing FasL involves the combination of the anti-inflammatory properties of IL-4 and the apoptosis of Fas(+) Mac1(+) granulocytes participating in the pathogenic process.
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PMID:Expression of Fas ligand improves the effect of IL-4 in collagen-induced arthritis. 1060 54

IL-18 is an important cytokine in autoimmune and inflammatory diseases through the induction of IFN-gamma, TNF-alpha, and IL-1. We report herein that collagen-induced arthritis (CIA) in mice is inhibited by treatment with murine IL-18 binding protein (mIL-18BP). CIA was induced in DBA/1J mice by the injection of bovine type II collagen (CII) in IFA with added Mycobacterium tuberculosis on days 0 and 21. The mice were then treated for 3 wk with PBS or with two doses of mIL-18BP (0.5 and 3 mg/kg) as a fusion protein with the Fc portion of murine IgG1. Both the clinical disease activity scores and the histological scores of joint damage were reduced 50% in mice treated with either dose of mIL-18BP. Proliferation of CII-stimulated spleen and lymph node cells as well as the change in serum levels of IgG1 and IgG2a Ab to collagen between days 21 and 42 were decreased in mice treated with mIL-18BP. The production of IFN-gamma, TNF-alpha, and IL-1beta in cultured spleen cells was reduced by in vivo treatment with low dose, but not high dose, mIL-18BP. FACS analysis showed a slight decrease in NK cells and an increase in CD4(+) T cells in spleens of mice treated with mIL-18BP. The steady state mRNA levels of IFN-gamma, TNF-alpha, and IL-1beta in isolated joints were all decreased in mice treated with both doses of mIL-18BP. The mechanisms of mIL-18BP inhibition of CIA include reductions in cell-mediated and humoral immunity to collagen as well as decreases in production of proinflammatory cytokines in the spleen and joints.
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PMID:Mechanisms of inhibition of collagen-induced arthritis by murine IL-18 binding protein. 1257 81

To explore the potential of baculovirus serving as a gene delivery vector in tissue engineering of articular cartilage, the efficiencies of baculovirus-mediated gene delivery into primary rat chondrocytes were evaluated and the transduction protocol commonly employed by others (using concentrated virus at multiplicity of infection [MOI] 200 for 1 h) was found to be ineffective (<1%). Therefore, a modified protocol was adopted, which markedly enhanced the efficiency (68%). Optimization of the transduction parameters, such as incubation time (8 h), temperature (25 degrees C), and surrounding solutions (PBS), further increased the efficiency to 88% and prolonged the duration of expression to 21 days, suggesting that the cells previously considered nonpermissive to baculovirus transduction may be reexamined for their permissiveness using alternative transduction protocols. The elevated efficiency correlated well with increased virus uptake upon extended incubation time, as demonstrated by quantitative real-time polymerase chain reaction (Q-PCR). The Q-PCR also revealed the degradation of viral DNA over culture time. Although the virus transduction somewhat hindered the cell proliferation, growth rate could be restored in the long-term culture. More importantly, transduced cells could secrete articular cartilage-specific type II collagen and glycosaminoglycan as well as mock-transduced cells, confirming that normal differentiation state of rat chondrocytes is retained upon baculovirus transduction. Taken together, these data indicate that baculovirus is a safe and highly efficient gene delivery vehicle into rat chondrocytes.
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PMID:Highly efficient baculovirus-mediated gene transfer into rat chondrocytes. 1547 27

We have reported that serum IL-6 level was related with the degree of anemia in monkey collagen-induced arthritis (CIA). In this study, we examined whether IL-6 blockade ameliorated an anemia in monkey CIA. CIA was induced by twice immunization of bovine type II collagen with adjuvant. When anemia became evident, anti-IL-6 receptor antibody, tocilizumab was intravenously injected once a week for 4 weeks. Controls received PBS in a same manner. Hematological and biochemical parameters were measured regularly and serum hepcidin-25 levels were measured by SELDI-TOF mass spectrometry. Moreover, hepcidin mRNA induction in Hep3B cells by serum from arthritic monkeys was examined by real-time PCR. Administration of tocilizumab rapidly decreased CRP levels and improved iron-deficient anemia within 1 week. Tocilizumab induced rapid but transient reduction in serum hepcidin-25. Hepcidin mRNA expression was more potently induced by serum from arthritic monkey and this was inhibited by the addition of tocilizumab. Blockade of IL-6 signaling rapidly improved anemia in monkey arthritis via the inhibition of IL-6-induced hepcidin production.
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PMID:Tocilizumab, a humanized anti-interleukin-6 receptor antibody, improved anemia in monkey arthritis by suppressing IL-6-induced hepcidin production. 1963 19

The alternative pathway (AP) of complement is required for the induction of collagen Ab-induced arthritis (CAIA) in mice. The objective of this study was to examine the effect of a recombinant AP inhibitor containing complement receptor 2 and factor H (CR2-fH) on CAIA in mice. CR2 binds to tissue-fixed activation fragments of C3, and the linked fH is a potent local inhibitor of the AP. CAIA was induced in C57BL/6 mice by i.p. injections of 4 mAb to type II collagen (CII) on day 0 and LPS on day 3. PBS or CR2-fH (250 or 500 microg) were injected i.p. 15 min after the mAb to CII on day 0 and 15 min after LPS on day 3; the mice were sacrificed on day 10. The disease activity score (DAS) was decreased significantly (p < 0.001) in both groups receiving CR2-fH compared with the PBS. Histology scores for inflammation, pannus, bone damage, and cartilage damage decreased in parallel with the DAS. C3 deposition in the synovium and cartilage was significantly reduced (p < 0.0001) in the mice treated with CR2-fH. In vitro studies with immune complexes containing type II collagen and mAb to CII showed that CR2-fH specifically inhibited the AP with minimal effect on the classical pathway (CP) and no effect on the lectin pathway (LP). The relative potency of CR2-fH in vitro was superior to mAbs to factor B and C5. Thus, CR2-fH specifically targets and inhibits the AP of complement in vitro and is effective in CAIA in vivo.
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PMID:Targeted inhibition of the complement alternative pathway with complement receptor 2 and factor H attenuates collagen antibody-induced arthritis in mice. 1982 24


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