Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study investigates the cellular and molecular mechanisms responsible for expressing genetic control of type II collagen-induced murine chronic arthritis. Analyses were made for both humoral and cellular immune responses, since the induction of arthritis required synergy between both types of immunities. Immunization of high (DBA/1) and low (C57BL/6, C3H/He, BALB/c) responder mice with native bovine type II collagen resulted in the production of the respective high and low levels of anti-collagen antibody. However, polyclonal in vitro stimulation of normal spleen cells from high or low responder mice with lipopolysaccharide (LPS) induced a comparable magnitude of anti-collagen antibody responses, indicating the localization of the genetic defect at cellular levels other than B cells themselves. In contrast to immunization with native collagen, sensitization of DBA/1 mice with heat-denatured collagen failed to stimulate B cells, but resulted in selective generation of L3T4+ T cell-mediated immunity. These included anti-collagen delayed-type-hypersensitivity (DTH) responses and the generation of various interleukins (IL) responsible for antibody production as well as DTH responses. It was demonstrated that there was appreciable difference in the magnitudes of these responses between lymphoid cells from high and low responder mice. Differential effects of sensitization with heat-denatured collagen in high versus low responders were reflected on the genetic difference in the development of chronic arthritis. A typical arthritis was induced neither in denatured collagen-sensitized DBA/1 mice nor in unsensitized mice transferred with anti-collagen antiserum. However, the antiserum transfer into denatured collagen-sensitized DBA/1 mice induced chronic perpetuating arthritis. This sharply contrasted with the failure of the same aliquot of the antiserum to induce a chronic arthritis when inoculated into denatured collagen-sensitized low responder mice. These results indicate that the genetic control of the induction of arthritis is expressed on L3T4+ T cells which are required for generating anti-collagen humoral as well as cell-mediated immunities as assessed by DTH responses in vivo or lymphokine productions in vitro.
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PMID:Type II collagen-induced murine arthritis. II. Genetic control of arthritis induction is expressed on L3T4+ T cells required for humoral as well as cell-mediated immune responses to type II collagen. 257 23

Human macrophages have been implicated in connective tissue remodeling; however, little is known about their direct effects upon collagen degradation. We now report that human alveolar macrophages in culture produced both a collagenase and a collagenase inhibitor. The collagenase was secreted in latent form and could be activated by exposure to trypsin. Collagenase production could be increased three- to fourfold by incubating the cells with lipopolysaccharide, but synthesis was largely unaffected by exposure to phorbol myristate acetate. By several criteria, macrophage collagenase was the same as the collagenase secreted by human skin fibroblasts: (a) they were antigenically indistinguishable in double immunodiffusion; (b) both degraded type III collagen preferentially to type I, had little activity against type II collagen, and none against types IV and V, and (c) their affinity for susceptible collagens was equivalent, Michaelis constant = 1-2 microM. Collagenase inhibitory activity was also present in the macrophage-conditioned medium, and was accounted for by an antigen that showed immunologic and functional identity with the collagenase inhibitor secreted by human skin fibroblasts. The amount of inhibitor released by unstimulated cells, approximately 100 ng/10(6) cells per 24 h, was substantially augmented by both phorbol and lipopolysaccharide, although considerable variability in response to these agents was observed between macrophage populations derived from different subjects. As negligible quantities of collagenase or collagenase inhibitor were detectable intracellularly, it appeared that both proteins were secreted rapidly after synthesis. Thus, human macrophages have the capacity to modulate collagen degradation directly by production of collagenase and collagenase inhibitor.
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PMID:Human alveolar macrophages produce a fibroblast-like collagenase and collagenase inhibitor. 299 37

The formation of an air pouch in the subcutaneous tissues of a rat previously inoculated intradermally with Freund's mycobacterial adjuvant for the induction of arthritis, provokes a marked but transient inflammatory reaction in the cavity lining of the pouch. The dependence of this reaction on arthritis development was investigated. It was found that rats inoculated with mycobacterial adjuvant by subcutaneous or intraperitoneal injection failed to produce either a pouch reaction or develop arthritis. Intradermal injections of carrageenan, mycobacteria (M. tuberculosis in saline), Freund's incomplete adjuvant alone or containing Salmonella typhimurium lipopolysaccharide and Bordetella pertussis organisms or mycobacterial adjuvant containing egg albumin were also ineffective. Intradermal injections of type II collagen in Freund's incomplete adjuvant did induce arthritis but no pouch reaction; however, this could be elicited after direct challenge with antigen. Pretreatment of rats intraperitoneally with saline suspensions of mycobacteria or a moderate dose of cyclophosphamide prevented both the pouch reaction and arthritis developing to intradermal mycobacterial adjuvant. Pretreatment of rats with mycobacteria was without effect on type II collagen-induced arthritis. From the results of this study it would appear that the air pouch reaction and arthritis induced by adjuvant are directly associated. The inability of collagen to induce a similar reaction demonstrates a fundamental dissimilarity with mycobacterial adjuvant in its mechanism of production of arthritis.
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PMID:Polyarthritis and the air pouch reaction: dissimilarity of adjuvant and collagen models. 337 28

The in vitro production of anti-bovine type II collagen antibodies by lymphocytes from rats immunised with native bovine type II collagen and adjuvant was measured using a solid-phase enzyme-linked immunoassay. Antibodies to native bovine type II collagen could be detected in culture supernatants from the lymphocytes of rats only if they had been immunised with native bovine type II collagen, but not if immunised with native type I collagen, with keyhole limpet haemocyanin, with buffer or if un-immunised. The antibodies produced also bound to native rat, human and chick type II collagens, to native bovine 1 alpha 2 alpha 3 alpha collagen but not to native type I collagen. The amount of antibody in the cultures was altered by the presence of serum from type II collagen immunised rats or by the presence of either cyclohexamide, colchicine, Concanavalin A, catalase or lipopolysaccharide. Pre-treatment of the lymphocytes with mitomycin-C reduced the amount of anti-collagen antibody. This system can be used to investigate mechanisms controlling anti-collagen antibody production.
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PMID:Collagen-induced arthritis: antibody production by lymphocytes in vitro. 360 68

Synovial fluid (SF) mononuclear cells (MNC) from 13 patients with rheumatoid arthritis (RA) and 12 patients with other arthritic diseases (OD) including osteoarthritis (OA), gout and spondyloarthritis (SA) were cultured in the presence of collagen types I and II or lipopolysaccharide (LPS) for 24 h. Interleukin-1 (IL-1), IL-6 and tumor necrosis factor-alpha (TNF-alpha) in the SF and culture supernatants were assayed using ELISA. The results showed that one-half of the RA patients with high SF monocyte count had high SF IL-6 levels that coincided with the high spontaneous release of IL-6 by SF MNC. In the other RA patients with lower SF monocyte count, type II collagen induced significantly higher IL-1 beta than the medium control levels by SF MNC (P < 0.01) or that of the other diseases (P < 0.01). Similarly, type II collagen-induced IL-6 and TNF-alpha production rose significantly (P < 0.01) from SF MNC of RA but less from OD (P < 0.05). In addition, type I collagen could also induce IL-1, IL-6 and TNF-alpha in these samples from RA and OD patients but was less potent than type II collagen. Our results indicate that collagen-induced cytokines may be important in the pathogenesis of the disease.
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PMID:Collagen induces cytokine production by synovial fluid mononuclear cells in rheumatoid arthritis. 762 81

Chronic inflammation and degradation of connective tissue in the course of periodontitis are maintained by bacterial products such as lipopolysaccharides (LPS), which probably act via inflammation mediators, e.g. cytokines. We investigated the effects of lipopolysaccharide (LPS) from E. coli and mouse recombinant interleukin 1 alpha (mrIL-1) on chondrogenesis, endochondral mineralization, matrix metalloproteinase activation and matrix degradation in vitro using cartilage organoid cultures. Mesenchymal cells of limb buds from mouse embryos (day 12) were grown at high density on a membrane filter at the medium/air interphase for 14 days. Chondrogenesis occurred during the first 6 days of culture. Endochondral mineralization took place upon addition of 5 mM beta-glycerophosphate from day 7 to 14. Treatment of the cultures with LPS and mrIL-1 on days 2 to 14 and during mineralization on days 7 to 14 resulted in a marked decrease of types I and II collagen, matrix mineralization and proteoglycan content. In the medium, proteoglycan content and metalloproteinase activity were enhanced. LPS induced IL-1 alpha production and release into the medium. LPS antagonist polymyxin B partly abolished the LPS effect, whereas IL-1 receptor antagonist (IL-1ra) partly abolished both LPS and mrIL-1 effects. Reversal of LPS-induced effects by IL-1ra was comparable to the reversal of mrIL-1 effects, only the decrease in type II collagen after LPS treatment was abolished to a lesser extent by IL-1ra.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction of metalloproteinase activity, cartilage matrix degradation and inhibition of endochondral mineralization in vitro by E. coli lipopolysaccharide is mediated by interleukin 1 alpha. 858 63

DBA/1 mice develop a chronic peripheral arthritis after immunization with type II collagen termed collagen-induced arthritis. We have localized the main arthritogenic determinants of CB11, a CNBr-generated arthritogenic fragment of chick type II collagen (CII), using 3 smaller peptide fragments of CB11 generated by endoproteinase LysC, LysC1 (CII 124-290), LysC2 (CII 291-374) and LysC3 (CII 375-402) and a panel of monoclonal antibodies (mAb) specific to CB11. MAb specific to the arthritogenic region of CB11 were also used to study the synergistic effect of E. coli lipopolysaccharide (LPS) on antibody-mediated arthritis in naive DBA/1 mice. LysC2 contained a minimum essential arthritogenic fragment of type II collagen: LysC2 induced arthritis by active immunization, also, a combination of four mAb specific to LysC2 passively transferred arthritis to naive mice. A single i.p. injection of LPS (50 micrograms/mouse) reduced the threshold values of the arthritogenic dose of mAb from 1 mg to 50 micrograms/clone per mouse, and decreased the number of mAb required for inducing arthritis from 4 to 2 clones. These observations suggest that LysC2, an 84 amino acid residue fragment, contains the main arthritogenic determinants within chick CB11. Importantly, LPS, a strong inducer of pro-inflammatory cytokines, negates the required multiple epitope specificity of autoantibodies in the passive transfer model and acts synergistically in the induction of arthritis by autoantibody.
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PMID:Collagen-induced arthritis in mice: synergistic effect of E. coli lipopolysaccharide bypasses epitope specificity in the induction of arthritis with monoclonal antibodies to type II collagen. 873 68

It is well known that T cells recognize antigen as processed peptides bound to major histocompatibility complex molecules on the surface of antigen-presenting cells. Recently, it has been shown that T cells can specifically recognize synthetic glycopeptides. However, whether glycopeptides are selected for presentation during antigen processing of glycoproteins and eventually elicit carbohydrate-specific T cells is still an open question. In this study, we utilized synthetic glycopeptides to analyze T cell recognition of the naturally glycosylated immunodominant peptide representing type II collagen (CII) residues 256-270. In this peptide, lysines at positions 264 and 270 may be post-translationally modified by hydroxylation and subsequent O-linked glycosylation with beta-galactosyl or alpha-glucosyl-(1-->2)-beta-galactosyl residues. T cell hybridomas established from type II collagen-immunized mice specifically recognized CII 256-270 with either galactose or glucosyl-galactose at position 264. The T cell hybridoma recognizing glucosyl-galactose displayed no cross-reactivity either to galactose or to the structurally different alpha-galactosyl-(1-->4)-beta-galactose. Furthermore, the T cell hybridoma recognizing galactose did not cross-react to glucosyl-galactose or galactosyl-galactose, indicating that the antigen-presenting cells (bulk spleen cells, lipopolysaccharide-stimulated spleen cells, anti-CD40-stimulated spleen cells, peritoneal exudate cells or CFA-primed lymph node cells) inefficiently processed carbohydrates when the antigen was given as a glycopeptide.
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PMID:Antigen processing and presentation of a naturally glycosylated protein elicits major histocompatibility complex class II-restricted, carbohydrate-specific T cells. 876 38

We have developed a new model of autoimmune arthritis in DBA/1 mice by feeding chick type II collagen (CII) for 2-3 week intervals over a 15 week period. Clinically evident arthritis occurred in 8/10 mice receiving native CII (nCII; 100 micrograms/mouse) alone at 9-13 weeks. Arthritis was aggravated by the further ingestion of CII, while remission occurred after withdrawal of the CII. Heat-denatured CII (dCII; 200 micrograms/mouse) was also arthritogenic if co-administered with ovoinhibitor (OVI; 2 mg/mouse), a proteinase inhibitor. Co-oral administration of lipopolysaccharide (LPS; 10 micrograms/mouse) with CII enhanced the antibody production and T-cell responses to CII, and induced a more chronic arthritis that progressed spontaneously without further administration of CII or LPS. Long-term oral administration of LPS alone also induced a mild arthritis characterized by destruction of bone rather than cartilage. These observations suggest that abnormal gastrointestinal absorption of dietary mimic antigens and intestinal bacterial toxins can potentially disrupt self-tolerance mechanisms, thereby precipitating or exacerbating autoimmune disease in genetically susceptible individuals.
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PMID:Induction by chronic autoimmune arthritis in DBA/1 mice by oral administration of type II collagen and Escherichia coli lipopolysaccharide. 881 Jun 65

KE-298 is a new immunomodulatory agent with a chemical structure similar to that of D-penicillamine. We compared the effects of KE-298 on type II collagen-induced arthritis (CIA) in mice with those of prednisolone. KE-298 at a dose of 25 mg/kg showed only a decrease in the progression of foot pad swelling. At doses of 50 and 100 mg/kg, however, KE-298 inhibited the severity and development of the collagen-induced arthritis index, the progression of foot pad swelling, bone damage and histopathological changes. These inhibitory effects were more pronounced at the dose of 50 mg/kg than at 100 mg/kg. KE-298 also significantly inhibited the delayed-type hypersensitivity (DTH) response to type II collagen, but did not affect the production of anti-type II collagen IgG antibody in arthritic mice. To determine the inhibitory mechanism of KE-298, we studied the effect of KE-298 on IL-1 beta and TNF-alpha production in mice. We found that KE-298 inhibited bacterial lipopolysaccharide (LPS)-induced IL-1 beta production at doses of 50 and 100 mg/kg. It inhibited the production of TNF-alpha at the dose of 50 mg/kg, but not at 100 mg/kg. In summary, at appropriate dosages, KE-298 inhibited CIA and TNF-alpha production in mice. KE-298 also inhibited the DTH reaction to type II collagen and LPS-induced IL-1 beta production in a dose-related fashion. These findings suggest that these effects of KE-298 are closely related to its immunomodulatory action.
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PMID:Effect of KE-298 on experimental arthritis in mice. 893 Nov 4


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