Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In Brown Norway (BN) rats, it is known to be difficult to induce experimental autoimmune uveoretinitis (EAU) by the injection of retinal S-antigen (S-Ag) or interphotoreceptor retinoid-binding protein (IRBP) together with complete Freund's adjuvant (CFA), unless intravenous Bordetella Pertussis is used as an additional adjuvant. In the present study it was found that the rate of onset of EAU could be increased in BN rats immunized with IRBP and CFA by simultaneous cryosurgery to the renal cortex. There was no evidence of retinal vasculitis, pinealitis or nephritis in the rats with EAU except for renal inflammatory infiltrates as a reaction to the cryosurgery. Affected eyes eventually showed destruction of most retinal components and prominent infiltration of the retina by macrophages, with the changes being more severe than those previously reported in Lewis rats with EAU induced by IRBP. Data suggesting the existence of an antibody that cross-reacts with the proximal renal tubules and the retinal pigment epithelium were also obtained.
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PMID:Experimental autoimmune uveoretinitis in brown Norway rats induced by bovine interphotoreceptor retinoid-binding protein and renal cryosurgery. 189 71

An EAU model has been developed in the mouse using the retinal soluble antigen (SAg), and the interphotoreceptor retinoid-binding protein (IRBP). Immunogenetic studies indicate that sensitivity to disease is H-2 dependent, but some data suggest that non-MHC genes may also contribute to the regulation of EAU. IRBP was a more potent uveitogen than SAg. Ability to mount lymphocyte and antibody responses was exhibited both by EAU-susceptible and by EAU-resistant strains, and could not be used as a predictive parameter. Dependence of disease induction on variables of immunization was studied in B10.A mice (I-Ak) immunized with IRBP. Use of Bordetella pertussis as additional adjuvant was a prerequisite for successful disease induction. Use of purified pertussis toxin (PTX), rather than a suspension of pertussis bacteria, allowed reduction of the immunization protocol to a single dose of IRBP in CFA. Severity and incidence of disease, as well as its clinical course, were directly affected by the dose of antigen and PTX, and could be controlled by varying their respective doses. A spectrum of disease, from hyperacute to chronic, could be obtained. The chronic type of EAU tended to relapse, with lesions reappearing after a brief period of essential quiescence. The special advantages of the murine EAU model for the study of ocular autoimmunity are discussed.
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PMID:The mouse as a model of experimental autoimmune uveoretinitis (EAU). 238 8

Experimental autoimmune uveoretinitis (EAU) in the mouse is a recently developed model of ocular autoimmunity. Dependence of disease induction on qualitative and quantitative parameters of immunization was studied in B10.A mice immunized with interphotoreceptor retinoid-binding protein (IRBP). It was found that use of Bordetella pertussis adjuvant as well as its mode of preparation was of critical importance for disease induction; no disease was induced if pertussis adjuvant was omitted. The minimal effective protocol for EAU induction when the vaccine form of B. pertussis adjuvant was used consisted of pretreatment with cyclophosphamide, two divided doses of IRBP in complete Freund's adjuvant (CFA), and two divided doses of B. pertussis vaccine. Any reduction in the immunization schedule resulted in reduced incidence of disease. In contrast, substituting purified B. pertussis toxin (PTX) for the vaccine allowed reduction of the immunization schedule to a single dose of IRBP in CFA and omission of the cyclophosphamide pretreatment. Severity and incidence of disease could be quantitatively controlled by varying the respective doses of IRBP and PTX. In addition, a chronic or an acute clinical course of EAU could be obtained by using either a low-dose or a high-dose immunization, respectively. Establishment of a single dose induction protocol and the quantitation of the immunopathogenic response as a function of the variables of immunization lay the foundation for the further development and utilization of this promising model of ocular autoimmunity.
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PMID:Experimental autoimmune uveoretinitis in mice. Induction by a single eliciting event and dependence on quantitative parameters of immunization. 239 17

Rats immunized with microgram amounts of interphotoreceptor retinoid-binding protein (IRBP), a glycoprotein which localizes specifically in the eye and pineal gland, developed uveoretinitis and pinealitis. The severity and onset of changes were found to be dose-related and to be enhanced by B. pertussis bacteria. In general, the inflammatory changes induced by IRBP resembled those provoked by S-antigen (S-Ag), but significant differences were noted between the two diseases. The possible usefulness of the new experimental autoimmune disease is discussed.
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PMID:Uveoretinitis and pinealitis induced by immunization with interphotoreceptor retinoid-binding protein. 348 97

Experimental autoimmune uveoretinitis (EAU) is an intraocular inflammatory disease model induced by retinal specific antigens such as S-antigen and interphotoreceptor retinoid-binding protein (IRBP). The present study was aimed at testing the uveitogenicity of IRBP and an IRBP-derived peptide in various strains of rats with different RT1 (major histocompatibility complex in rats) haplotypes. Immunization with IRBP induced distinct EAU in LEW (RT1l), WKAH (RT1k) W/M (RT1k), LEJ (RT1j), and BUF (RT1b) rats. IRBP also induced a low grade of EAU in SDJ (RT1u), but no disease was detected in TO rats, another strain of the RT1u haplotype. IRBP-derived peptide R16 (aa 1177-1191) induced severe EAU in LEW rats and moderate disease in the WKAH and W/M strains. Immunization with R16 also induced low levels of inflammation in eyes of 75% and 20% of LEJ and BUF rats, respectively, but this peptide did not cause any disease in SDJ and TO rats. Injection of Bordetella pertussis had minimum or no effect on the induction of EAU by peptide R16 in this study. These data thus indicate that peptide R16 can bind to various RT1 molecules in addition to RT1l. Further, our observations support the notion that certain epitopes of IRBP could be uveitogenic in humans with different HLA haplotypes.
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PMID:Interphotoreceptor retinoid-binding protein derived peptide can induce experimental autoimmune uveoretinitis in various rat strains. 785 Nov 21

S-antigen or interphotoreceptor retinoid-binding protein (IRBP), when injected with Freund's complete adjuvant into mice, does not easily cause experimental autoimmune uveoretinitis (EAU). In this report, we describe the results of injecting IRBP with Freund's complete adjuvant, together with the intraperitoneal administration of Bordetella pertussis, into several types of congenic mice (B10, B10A, B10BR, B10D2). These congenic mice, of C57BL/10 (B10) origin, differ at the H-2 locus on chromosome 17. We were able to produce EAU in 38.5% of B10A mice, and 12.5% of B10BR mice, confirming that EAU can develop in these mice that carry the k genotype at the K, I-A, and I-E regions of the major histocompatibility complex (MHC) H-2 locus. We believe that the k genotype of the K, I-A, and I-E regions is important as a factor in the pathogenesis of EAU in congenic B10 mice.
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PMID:[An investigation of factors in the pathogenesis of experimental autoimmune uveoretinitis (EAU) in congenic mice]. 794 37

Pertussis toxin (PTX) has been widely used as an adjuvant to induce Th1-mediated organ-specific autoimmune diseases in animal models. However, the cellular and molecular mechanisms remain to be defined. In this study, we showed that dendritic cells (DC) stimulated with PTX (PTX-DC) were able to substitute for PTX to promote experimental autoimmune uveitis (EAU). EAU induced by PTX-DC revealed a typical Th1 response, characterized by high uveitogenic retinal Ag interphotoreceptor retinoid-binding protein (IRBP)-specific IFN-gamma and IL-12 production in the draining lymph nodes, as well as increased levels of anti-IRBP IgG2a and decreased levels of anti-IRBP IgG1 in the serum of IRBP-immunized mice. Furthermore, PTX-DC preferentially induced T cells to produce the Th1 cytokine, IFN-gamma. After being stimulated with PTX, DC exhibited up-regulation of MHC class II, CD80, CD86, CD40, and DEC205. PTX-DC had also increased allostimulatory capacity and IL-12 and TNF-alpha production. Serum IL-12 was increased in naive mice that received PTX-DC i.p. In addition, PTX activated extracellular signal-regulated kinase in DC. Following the inhibition of extracellular signal-regulated kinase signaling, the maturation of PTX-DC was reduced. Subsequently, the ability of PTX-DC to promote IFN-gamma production by T cells in vitro and to induce EAU in vivo was blocked. The results suggest that PTX might exert an adjuvant effect on DC to promote their maturation and the production of proinflammatory cytokines, thereby eliciting a Th1 response.
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PMID:Pertussis toxin enhances Th1 responses by stimulation of dendritic cells. 1257 36

Endogenous interferon (IFN)-gamma negatively regulates experimental autoimmune uveoretinitis (EAU), a Th1-mediated disease. Although it is well known that IFN-gamma exerts its effects by binding to the IFN-gamma receptor (IFN-gammaR), the role that IFN-gammaR plays in the development of EAU has not been investigated. Fyn has been reported to inhibit Th2 differentiation. We aimed to investigate how endogenous IFN-gammaR and fyn, which influence Th1/Th2 differentiation, participate in the development of EAU. Sex-matched 6- to 10-week-old C57BL/6 wild-type (WT), IFN-gammaR knockout (GRKO) and fyn knockout (fyn KO) mice were compared. Mice were immunized subcutaneously with human interphotoreceptor retinoid-binding protein peptide 1-20 emulsified in Freund's complete adjuvant together with an intraperitoneal injection of Bordetella pertussis toxin. Three weeks later, mice were sacrificed, and their eyes and spleens were harvested for histopathologic analyses and examination of cellular immune responses, respectively. Cellular immune responses were evaluated by measuring the proliferative responses and cytokine production [interleukin (IL)-4, IL-5, IL-6, IL-13, IFN-gamma and tumor necrosis factor (TNF)-alpha] of splenocytes. The incidence of EAU was 40.0% in WT mice, 59.3% in GRKO mice and 78.6% in fyn KO mice. The average EAU score was 0.294 in WT mice, 0.917 in GRKO mice and 1.063 in fyn KO mice. Upon EAU induction, significant infiltration of eosinophils into the eyes was observed in GRKO and fyn KO mice compared to WT mice. Splenocytes from GRKO mice proliferated against the antigen and a mitogen more vigorously than those from WT and fyn KO mice. Stimulation of splenocytes with the antigen induced a higher production of IL-4, IL-6, IL-13 and IFN-gamma in GRKO mice compared to WT and fyn KO mice. In contrast, IL-5 and TNF-alpha were most abundantly produced by splenocytes from fyn KO mice compared to WT and GRKO mice. The incidence and mean severity of EAU were significantly higher in GRKO and fyn KO mice than in WT mice, suggesting that endogenous IFN-gammaR and fyn negatively regulate the development of EAU. The different cytokine production patterns by the GRKO and fyn KO mice indicate that the negative regulatory mechanism mediated by IFN-gammaR and fyn may differ.
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PMID:Mice lacking the IFN-gamma receptor or fyn develop severe experimental autoimmune uveoretinitis characterized by different immune responses. 1590 35