Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Native type II collagen, the major cartilage collagen, is immunogenic and arthritogenic in rodents. To investigate whether minor cartilage collagens are arthritogenic, we immunized DBA/1 mice with the pepsin-soluble fractions of type IX or type XI collagen emulsified in Freund's complete adjuvant. Both collagens were arthritogenic in DBA/1 mice after only 1 injection. However, the incidence of the polyarthritis was lower and the severity was lesser than with that induced by bovine type II collagen, even when a booster injection was administered. All mice developed a humoral response to the immunizing antigen, without any relationship to the arthritic status. Interestingly, competition experiments showed that antibodies raised against type XI collagen also bound with high avidity to type II collagen. In contrast, sera from type IX collagen-immunized mice did not react with either type II or type XI collagen. We conclude that types IX and XI minor cartilage collagens are both arthritogenic and immunogenic in DBA/1 mice. Whether the recognition of epitopes common to different collagens is relevant to the articular pathology remains to be elucidated.
Arthritis Rheum 1990 Jan
PMID:Arthritogenicity of minor cartilage collagens (types IX and XI) in mice. 230 60

We previously reported that treatments with human recombinant interleukin-1 beta (rIL-1 beta) in DBA/1 mice which were suboptimally immunized with native chick type II collagen (NcII) markedly accelerated the onset of collagen-induced arthritis (CIA). In the present study, we further characterized this IL-1-mediated enhancement of murine arthritis by examining the in vivo effects of rIL-1 beta in another arthritis model, namely, the spontaneous arthritis of the MRL/lpr mouse strain. The results of these studies demonstrated that IL-1 treatments also enhanced the onset and progression of the spontaneous arthritic disease in MRL/lpr mice. A substantial proportion of the IL-1-treated MRL/lpr mice that were between 3 and 3.5 months of age exhibited swelling in either the hind or front paws. Moreover, histopathologic studies demonstrated the presence of striking alterations within the various joints of these IL-1-treated MRL/lpr mice. Such abnormalities were not detected in the non-IL-1-treated, age-matched MRL/lpr mice. Therefore, as in the experimentally induced disease of CIA, IL-1 may also be capable of contributing to the pathogenesis of the spontaneous arthritis of MRL/lpr mice.
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PMID:Interleukin 1 enhances the development of spontaneous arthritis in MRL/lpr mice. 230 78

The humoral function of the pineal gland is known to be strongly dependent on environmental lighting. Melatonin, the best characterized of the photo-dependent pineal hormones, has been reported to affect immune responses in mice. It has been hypothesized that the development of some types of psychosomatic and autoimmune diseases could be due to a disturbed release of this hormone. The present investigation was performed in order to evaluate effects of constant darkness (physiological stimulation of pineal melatonin synthesis) and constant light (physiological suppression of pineal melatonin synthesis) on the course of an experimental autoimmune model, the type II collagen-induced arthritis (CIA) in DBA/1 female mice. Mice kept in darkness develop more severe arthritis than those kept in constant light or in a normal dark/light rhythm (12 h light/12 h dark). Levels of anti-type II collagen antibodies were higher in mice kept in darkness, and the spleens of these animals were enlarged. Since castration of female DBA/1 mice enhances the severity of CIA, and since melatonin is known to exert effects on gonadal function, the experiment was repeated using oophorectomized mice. The same difference in arthritis severity between darkness- and light-exposed mice was obtained in this second experiment. We conclude that the exacerbation of arthritis in darkness is due to a darkness-induced change in levels of critical neurohumoral compound(s), that via gonadal independent mechanisms affect the autoimmune response. The exaggerated severity and chronicity of arthritis may be due to higher levels of melatonin in these animals.
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PMID:Constant darkness enhances autoimmunity to type II collagen and exaggerates development of collagen-induced arthritis in DBA/1 mice. 231 59

Immunization of castrated female DBA/1 mice with rat type II collagen (CII) induces severe polyarthritis with an onset 3-5 weeks after immunization and with 80-100% incidence. Estrogen treatment, inducing physiological 17 beta-estradiol (E2) levels, during a limited period before and after the immunization, or during another period before the expected onset of arthritis, delayed the arthritic onset by approximately 10 days but did not affect the incidence of severity of arthritis. Treatment with physiological doses of E2 after onset of arthritis decreased severity and duration of disease. The T-cell dependent anti-CII autoantibody response was suppressed if the E2 treatment was given immediately before and after CII immunization and was not significantly affected if E2 treatment was given after CII immunization. Neither the total anti-CII Ig levels nor the anti-CII IgG2a levels correlated with development of arthritis. We also titrated the serum levels of estrogen and recorded the vaginal smear response after injections of various doses of E2. This enabled us to work in a physiological range of estrogen levels, spanning the levels found at the end of pregnancy and those found during the normal estrous cycle. These levels were found to suppress antigen-specific T-cell functions but enhance certain B-cell activities since the delayed type hypersensitivity (DTH) reaction against CII was suppressed while the total number of splenic Ig-secreting cells increased. These findings suggest that estrogen in physiological doses is therapeutic for the development of collagen-induced arthritis and that estrogen exerts dualistic effects on the immune system by suppressing T-cell functions and stimulating certain B-cell activities. The suppressive effect on arthritis could not be explained by suppression of anti-CII autoantibody response and must therefore depend on other T-cell-mediated functions.
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PMID:Estrogen induced suppression of collagen arthritis. V: Physiological level of estrogen in DBA/1 mice is therapeutic on established arthritis, suppresses anti-type II collagen T-cell dependent immunity and stimulates polyclonal B-cell activity. 239 19

Purified chick type II collagen was cleaved with cyanogen bromide (CB), and the resulting peptides isolated and renatured. Sera from arthritic DBA/1 mice, immunized with chick type II collagen, were tested for reactivity with each peptide. The sera preferentially recognized peptides 11, 10, and 8, in that order. Some reactivity was also detected to peptides 9, 7, and 12. Because arthritis depends upon binding of antibody to autologous type II collagen in the joint, sera were also tested for reactivity with mouse type II collagen. There was a strong positive correlation between reactivity with peptide 11 and reactivity with mouse collagen, but no correlation was found with any of the other peptides. Peptides 11, 10, and 8 were also used for immunization. Antibodies were detected in response to each of these peptides, but arthritis developed only in mice immunized with peptide 11. We conclude that a major immunogenic and arthritogenic epitope on type II collagen resides in the region of the molecule represented by CB peptide 11.
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PMID:Collagen-induced arthritis in mice. Localization of an arthritogenic determinant to a fragment of the type II collagen molecule. 241 May 32

Collagen type II-specific long-term cultured T helper cells, derived from the DBA/1 mouse, have been established and characterized. Clones from these T-cell lines could be shown to recognize either species-specific or species-nonspecific determinants on the collagen type II molecule, including determinants on autologous mouse collagen. Induction of arthritis via transfer to both irradiated and normal syngeneic recipient mice was obtained with both collagen type II-specific T-cell lines and an autoreactive and collagen type II-specific T-cell clone. Fewer cells were needed to evoke arthritis in normal than in irradiated recipients. Cells from lines and the clone used for transfer were by immunocytochemistry shown to have T helper phenotype.
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PMID:T lymphocytes in collagen II-induced arthritis in mice. Characterization of arthritogenic collagen II-specific T-cell lines and clones. 241 28

Mice of the DBA/1 strain develop arthritis after immunization with native chick type II collagen. Although both a humoral and a cell-mediated response specific to type II collagen are associated with the disease, the underlying immunologic basis remains to be established. As an initial step to analyzing the involvement of cellular immunity in collagen-induced arthritis, we isolated and characterized T cell lines and clones specific to type II collagen. Two sets of T cell lines were obtained by limiting dilution. One set was found to react exclusively with denatured type II collagen, whereas the other set responded to both native and denatured type II collagen. The specificity of such T cells was demonstrated by their inability to respond to other soluble proteins such as type I collagen, HGG, KLH, or OVA. Cells from these lines recognized type II collagen only in an MHC (H-2q)-restricted fashion. Furthermore, the collagen-specific T cells were found to respond to type II collagens obtained from various species, including chick, bovine, and rat. Finally, each set of cells displayed a phenotype characteristic of T helper cells, namely Thy-1+, L3T4+, Lyt-2-.
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PMID:Murine T cells reactive to type II collagen. I. Isolation of lines and clones and characterization of their antigen-induced proliferative responses. 241 30

DBA/1 mice immunized with native chick type II collagen (NcII) emulsified in complete Freund's adjuvant develop arthritis, whose underlying mechanisms are still undefined. As an initial step to studying the role of T cells in collagen-induced arthritis (CIA), we have established T cell lines specific to type II collagen. Characterizations of the antigen-induced proliferative responses mediated by these T cells have been reported. In essence, two major populations of collagen-reactive T cells were isolated: those that responded mainly to denatured type II collagen (DcII) and another group that reacted with both DcII and NcII. As shown in the present study, all of the collagen-reactive T cell lines isolated were found to be functional, although they differed in their capacity to mediate helper activities assessed by different assays. Hence, both populations of T cells exhibited the ability to trigger B cell proliferation, whereas only the population that recognized both DcII and NcII was capable of activating the synthesis of immunoglobulins by B cells. T cells from this latter group also provided specific help for the generation of a secondary anti-DNP antibody response. In addition, these T cells were capable of activating NcII-specific B cells to produce anti-collagen antibodies. By contrast, the T cell lines that reacted exclusively to DcII failed to mediate such specific helper functions. The inability of such T cells to activate DNP-primed B cells upon challenge with DNP-DcII did not appear to be due to a modification of antigenic sites on DcII by haptenation. Inasmuch as the DcII-specific T cell lines also proliferate less well in response to DcII than the T cell lines that recognize both DcII and NcII, a difference in the nature of the antigen receptors expressed by the two populations of collagen-specific T cells may partly explain the above observations. However, the inability to generate appropriate factors required for further differentiation of B cells to produce antibodies may also account for the failure of DcII-specific T cells to activate DNP-primed B cells. Finally, both populations of T cells were capable of mediating specific delayed-type hypersensitivity response.
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PMID:Murine T cells reactive to type II collagen. II. Functional characterization. 241 31

A T cell line specific to human type II collagen (CII) was selected and propagated from DBA/1J mice immunized with human CII. The line cells were not reactive to type I or type III collagen of human origin, but they were cross-reactive to bovine, rat, and rabbit CII and they recognized both native and heat-denatured human CII. The cells were reactive to an N-terminal three-quarters fragment of human CII, produced by tadpole collagenase digestion of human CII, but not to a C-terminal one-quarter fragment of human CII. The cells showed Thy-1+, Lyt-1+, Lyt-2-, and L3T4+ phenotypes characteristic of T helper cells or delayed-type hypersensitive cells, determined by the immunofluorescence method. To clarify the role of T cells in the pathogenesis of collagen-induced arthritis, we inoculated this cell line into DBA/1J mice and found that they developed clinical arthritis, albeit at a low incidence. The cells attenuated by x-ray were capable of inducing resistance to the subsequent induction of collagen-induced arthritis of DBA/1J mice. The sera from mice protected by inoculation of the cell line exhibited anti-idiotypic antibody response against conventional and monoclonal anti-CII antibodies. Anti-T cell receptor response may be involved in the mechanism for the protective effect of the cell line against autoimmune murine arthritis.
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PMID:Isolation of T cell line capable of protecting mice against collagen-induced arthritis. 244 73

Immunization of mice with type II collagen (CII) leads to the production of anti-CII antibodies and, in susceptible strains, to the induction of arthritis. Specifically purified anti-CII antibodies from arthritic DBA/1 mice were used to prepare a rabbit anti-idiotypic antiserum. This antiserum recognizes a cross-reactive idiotype (CRI) present on 20-25% of anti-CII antibodies from DBA/1 mice immunized with bovine CII. The CRI is not present on DBA/1 anti-trinitrophenyl, undetectable in normal Ig and not Igh allotype linked. The presence of this CRI was examined after antigen specific suppression of the anti-CII antibody response by intravenous administration of chick or bovine CII. While intravenous injection of bovine CII, prior to immunization with chick CII, greatly reduces both the incidence of arthritis and the anti-CII response, the fraction of anti-bovine CII which expresses the CRI is increased by this treatment. These findings suggest that the CRI characterizes a disease-unrelated fraction of anti-CII which recognizes bovine and chick CII, but probably not mouse CII. In addition, attempts at idiotypic regulation of arthritis incidence and antibody response by in vivo administration of anti-idiotypic serum also indicate that the CRI-bearing antibody is not important for the induction of arthritis.
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PMID:A cross-reactive idiotype on anti-collagen antibodies in collagen-induced arthritis: identification and relevance to disease. 245 21


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