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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exposure of Wistar rats to the immunotoxic compounds hexachlorobenzene (HCB), bis(tri-n-butyltin)oxide, and benzo(a)pyrene was previously found to affect mRNA expression of interleukin (IL)-2, IL-2R alpha-chain, and interferon (IFN)-gamma, the prototypic Th1 cytokine. In contrast, the mRNA expression of IL-4, the prototypic Th2 cytokine, was unaffected. This latter finding suggested that the IL-4 mRNA expression may not be an unequivocal parameter for Th2 responses in the rat. In order to obtain such a parameter the present study was performed, consisting of two types of experiments. Expression and production of IL-4 as well as IL-10, a second Th2 cytokine, were measured. First, Lewis (Th1 prone) and Brown Norway (BN; Th2 prone) rats were exposed to HCB. Exposure was previously found to increase the serum immunoglobulin (Ig)E levels, an IL-4-dependent response, in BN but not Lewis rats, and in Lewis rats to aggravate experimental allergic encephalomyelitis (EAE), severity being inversely related to IL-10 levels. Secondly, BN rats were infected with Trichinella spiralis, an infection previously found to induce IL-4 production. HCB exposure did not affect IL-4 mRNA expression in either strain, while IL-4 production was decreased in Lewis and unaffected in BN rats. In Lewis rats both the mRNA expression and the production of IL-10 were decreased. The T. spiralis infection induced IL-4 and IL-10 mRNA expression, as well as IL-10 production. In contrast, the IL-4 production was strongly reduced. Thus, both the IL-10 mRNA expression and production correlated with the EAE development and T. spiralis infection. In HCB exposed Lewis rats and T. spiralis infected BN rats the IL-4 mRNA expression correlated with IgE levels and T. spiralis infection, respectively, whereas the IL-4 production lacked correlation in all cases. Collectively, these results suggest that IL-10 is an unequivocal Th2 parameter in the rat, whereas IL-4 is not.
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PMID:Interleukin-10 is an unequivocal Th2 parameter in the rat, whereas interleukin-4 is not. 1111 53

The level of CD45RC expression differentiates rat CD4 T cells in two subpopulations, CD45RC(high) and CD45RC(low), that have different cytokine profiles and functions. Interestingly, Lewis (LEW) and Brown Norway (BN) rats, two strains that differ in their ability to mount type 1 and type 2 immune responses and in their susceptibility to autoimmune diseases, exhibit distinct CD45RC(high)/CD45RC(low) CD4 T cell ratios. The CD45RC(high) subpopulation predominates in LEW rats, and the CD45RC(low) subpopulation in BN rats. In this study, we found that the antiinflammatory cytokines, IL-4, IL-10, and IL-13, are exclusively produced by the CD45RC(low) CD4 T cells. Using bone marrow chimeras, we showed that the difference in the CD45RC(high)/CD45RC(low) CD4 T cell ratio between naive LEW and BN rats is intrinsic to hemopoietic cells. Furthermore, a genome-wide search for loci controlling the balance between T cell subpopulations was conducted in a (LEW x BN) F(2) intercross. Genome scanning identified one quantitative trait locus on chromosome 9 (approximately 17 centiMorgan (cM); log of the odds ratio (LOD) score 3.9). In addition, two regions on chromosomes 10 (approximately 28 cM; LOD score 3.1) and 20 (approximately 40 cM; LOD ratio score 3) that contain, respectively, a cytokine gene cluster and the MHC region were suggestive for linkage. Interestingly, overlapping regions on these chromosomes have been implicated in the susceptibility to various immune-mediated disorders. The identification and functional characterization of genes in these regions controlling the CD45RC(high)/CD45RC(low) Th cell subpopulations may shed light on key regulatory mechanisms of pathogenic immune responses.
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PMID:The balance between CD45RChigh and CD45RClow CD4 T cells in rats is intrinsic to bone marrow-derived cells and is genetically controlled. 1120 43

Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune disease induced in susceptible rat strains by a single immunization with myelin basic protein (MBP). The Lewis (LEW) strain is susceptible to disease induction while the Brown Norway (BN) strain is resistant. This resistance involves non-MHC genes since congenic BN-1L rats, with LEW MHC on a BN-derived background, are also resistant. In the present study we show that, upon immunization with MBP, the non-MHC-encoded resistance to develop clinical EAE in BN-1L rats is associated with a decreased production of IFN-gamma. This may be due to a difference between LEW and BN-1L rats in their ability to produce regulatory cytokines such as IL-4, IL-10 and TGF-beta. In comparison to LEW rats, immune lymph node cells from BN-1L rats express an increased amount of IL-4 mRNA but produce less IL-10. Furthermore, the sera from BN-1L rats contain higher amounts of active TGF-beta1. Therefore, we have investigated the involvement of IL-4 and TGF-beta in the resistance of BN-1L rats to develop EAE using neutralizing mAb. Neutralization of TGF-beta, but not IL-4, renders BN-1L rats susceptible to clinical EAE without affecting the proliferation or the cytokine repertoire of immune lymph node cells. With respect to the origin of the endogenous TGF-beta production, we excluded the involvement of CD8 T cells and discuss a possible role of platelets and of CD4 T cells exhibiting the CD45RC(low) phenotype.
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PMID:Essential role of TGF-beta in the natural resistance to experimental allergic encephalomyelitis in rats. 1129 38

Intravenous immunoglobulin (IVIg) was shown to decrease the severity of acute graft-versus-host disease (aGVHD) in recipients of allogeneic bone marrow transplants. To investigate the mechanisms involved in the protective effect of IVIg, we have used the parent-into-F1 model in which parental lymphocytes are transferred into semi-syngeneic non-irradiated F1 rats. Here we report that IVIg, as well as F(ab')(2) fragments of IVIg, protected (Lewis x Brown-Norway) F1 rats against aGVHD induced by a single injection of Lewis lymphocytes. IVIg was given as five consecutive daily injections, starting on the day preceding that of the transfer of Lewis cells. Protection was associated with a decreased ability of lymphocytes to spontaneously proliferate and to produce NO and IFN-gamma, in the absence of an increased production of IL-10. We further demonstrate that protection was associated with a decrease in CD4(+) T cells bearing the activation marker CD134 in vivo, and with an enhanced apoptosis of activated CD4(+) T cells by IVIg, in vitro. Our observations suggest that the prevention of aGVHD by IVIg in this model is mediated by the induction of apoptosis of activated alloreactive CD4(+)CD134(+) donor T cells. The results further emphasize the role of normal immunoglobulin in modulating alloantigen immune responsiveness.
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PMID:Normal IgG protects against acute graft-versus-host disease by targeting CD4(+)CD134(+) donor alloreactive T cells. 1153 77

The present study was undertaken to elucidate the participation of Th1 and Th2 responses in granulomatous inflammation induced by Cryptococcus neoformans using Lewis and Brown Norway rats which have Th1-polarized and Th2-polarized innate immunity, respectively. Both strains demonstrated granulomatous inflammation in the lung, and the lesions were composed mainly of mononuclear phagocytes and surrounded by lymphocytes. Lewis rats demonstrated tuberculoid epithelioid cell granulomas with a central necrosis resembling caseation, and increased transcription of Th1 relevant cytokines. On the other hand, Brown Norway rats showed mature granulomas including eosinophils with increased transcription of IL-12 without increased transcription of not only IFN-gamma and IL-2 but also Th2 cytokines such as IL-4, IL-5, and IL-10, unexpectedly. The colony-forming unit of the lung was decreased exponentially in both strains, and that of Brown Norway rats was significantly lower than that of Lewis rats 10 days after the inoculation. This indicated that Brown Norway rats demonstrated more fungicidal activity than Lewis rats in the early stage of the infection. The role of eosinophils with humoral immunity may be considered to be resistant in Brown Norway rats in addition of the function of macrophages.
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PMID:Granulomatous and cytokine responses to pulmonary Cryptococcus neoformans in two strains of rats. 1167 86

1. We examined the effect of SP100030, a novel inhibitor of activator protein-1 (AP-1) and nuclear factor (NF)-kappa B transcription factors, in a rat model of asthma. 2. Sensitized Brown-Norway rats were treated with SP100030 (20 mg kg(-1) day(-1) for 3 days) intraperitoneally prior to allergen challenge. Allergen exposure of sensitized rats induced bronchial hyperresponsiveness (BHR), accumulation of inflammatory cells in bronchoalveolar lavage (BAL) fluid, and also an increase in eosinophils and CD2(+), CD4(+) and CD8(+) T-cells in the airways together with mRNA expression for IL-2, IL-4, IL-5, IL-10, and IFN-gamma. 3. Pre-treatment with SP100030 inhibited BAL lymphocyte influx (P<0.03), specifically reduced CD8(+) T-cell infiltration in the airway submucosa (P<0.03), and mRNA expression for IL-2, IL-5, and IL-10 (P<0.05). Neutrophil, eosinophil, and CD4(+) T-cells accumulation in the airways and BHR were not affected by SP100030. 4. Our results indicate that suppression of IL-2 and IL-5 mRNA expression may not necessarily lead to suppression of BHR. The expression of IL-5 mRNA may contribute to the airway accumulation of eosinophils, but does not correlate with the extent of eosinophilia. 5. The joint AP-1 and NF-kappa B inhibitor, SP100030, selectively inhibits CD8(+) T-cells, and mRNA expression of both Th1 and Th2 cytokines in vivo, but does not inhibit allergen-induced airway eosinophilia and BHR.
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PMID:A novel transcription factor inhibitor, SP100030, inhibits cytokine gene expression, but not airway eosinophilia or hyperresponsiveness in sensitized and allergen-exposed rat. 1168 51

To better understand asthma pathogenesis, we characterized airway responsiveness, lung inflammation, and mediator production of alveolar macrophages (AM) after allergen sensitization and challenge in two strains of rats showing different susceptibilities in developing airway allergic reactions. Airway responsiveness to acethylcholine was measured 24 h after ovalbumin (OVA) challenge, whereas bronchoalveolar lavages were performed 5 min, 8 h, and 24 h after challenge. Brown Norway rats showed airway hyperresponsiveness after challenge, whereas lung resistance remained unchanged in Sprague-Dawley rats. Interestingly, Sprague-Dawley rats developed a neutrophilic inflammation, whereas both neutrophils and eosinophils were increased in Brown Norway rats. AM mediator production varied with time with a lower tumor necrosis factor (TNF) and interleukin (IL)-10 release at 8 h after challenge. OVA challenge stimulated spontaneous TNF and IL-10 release by AM isolated 24 h after challenge in both strains of rats, although AM from Brown Norway rats released significantly more IL-10 and TNF. Furthermore, nitric oxide production was increased only in OVA-challenged (24 h) Brown Norway rats. Our results suggest that AM may participate to the expansion of Th2 inflammation in Brown Norway rats and that differences in AM mediator production may explain, in part, distinct allergic susceptibilities in these two strains of rats.
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PMID:Characterization of lung hyperresponsiveness, inflammation, and alveolar macrophage mediator production in allergy resistant and susceptible rats. 1197 Sep 10

Adjuvant arthritis (AA) is an experimental model of autoimmune arthritis that can be induced in susceptible strains of rats such as inbred Lewis upon immunization with CFA. AA cannot be induced in resistant strains like Brown-Norway or in Lewis rats after recovery from arthritis. We have previously shown that resistance to AA is due to the presence of natural as well as acquired anti-heat shock protein (HSP) Abs. In this work we have studied the fine specificity of the protective anti-HSP Abs by analysis of their interaction with a panel of overlapping peptides covering the whole HSP molecule. We found that arthritis-susceptible rats lack Abs to a small number of defined epitopes of the mycobacterial HSP65. These Abs are found naturally in resistant strains and are acquired by Lewis rats after recovery from the disease. Active vaccination of Lewis rats with the protective epitopes as well as passive vaccination with these Abs induced suppression of arthritis. Incubation of murine and human mononuclear cells with the protective Abs induced secretion of IL-10. Analysis of the primary and tertiary structure of the whole Mycobacterium tuberculosis HSP65 molecule indicated that the protective epitopes are B cell epitopes with nonconserved amino acid sequences found on the outer surface of the molecule. We conclude that HSP, the Ag that contains the pathogenic T cell epitopes in AA, also contains protective B cell epitopes exposed on its surface, and that natural and acquired resistance to AA is associated with the ability to respond to these epitopes.
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PMID:Resistance to adjuvant arthritis is due to protective antibodies against heat shock protein surface epitopes and the induction of IL-10 secretion. 1205 66

Obliterative bronchiolitis (OB) affects over half of all chronic human survivors following lung or heart-lung transplantation. Respiratory epithelial cell injury, peribronchial inflammation, and proliferation of fibrovascular connective tissue causing airway occlusion characterize this lesion. Using a rat model of experimental OB, tracheas and mainstem bronchi from Brown-Norway or Lewis (LEW) rats were transplanted subcutaneously into LEW recipients. At 7 days, airway lumens of allografts showed minimal luminal obstruction but significant respiratory epithelial loss. By 14 days, allografts demonstrated marked peribronchial inflammation, nearly complete loss of respiratory epithelium, and extensive intraluminal proliferation of fibrovascular connective tissue, with a mean 58% reduction in airway cross-sectional diameter. However, isografts showed only limited peribronchial inflammation and no loss of airway lumen. When recipients of allotransplants were treated with anti-IL-10, OB developed more rapidly. As early as 7 days, there was marked histologic evidence of OB and a 43% reduction in mean cross-sectional area. Allograft animals that received 5 microg/day of recombinant IL-10 as a constant infusion on day 14 showed almost complete preservation of respiratory epithelium and only mild peribronchial inflammation with only a 15% reduction in airway cross-sectional area. These findings suggest that endogenous IL-10 plays a regulatory role in the development of experimental OB.
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PMID:Regulatory role of IL-10 in experimental obliterative bronchiolitis in rats. 1256 91

Heavy metals induce various immunopathological disorders including an increase in serum IgE concentration in predisposed humans. The effects of HgCl2 or gold salts differ depending on the strain of rats tested: they induce Th2-mediated immunopathology in Brown-Norway (BN) rats while HgCl2 triggers an immunosuppression in Lewis (LEW) rats. The disease is due to the emergence of self-MHC class II reactive Th2 cells in BN rats. Autoreactive T cells are also found in HgCl2-injected LEW rats but they produce TGFbeta and IL-10 and have immunoregulatory properties. Hg or Au act on the early steps of T cell activation resulting in IL-4 and IFNgamma gene expression with preferential IL-4 expression in BN rats. Analyzing the effects of HgCl2 on T cells led us to identify a new signaling pathway implicated in IL-4 production. An important feature of this model concerns genetics. Indeed Th2-dependent autoimmunity induced by metals occurs only in BN rats that are genetically committed to develop Th2 responses. Cellular features at play are discussed as well as the identification of loci that control both the Th1/Th2 balance and susceptibility to autoimmunity.
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PMID:Th2-type immunopathological manifestations induced by mercury chloride or gold salts in the rat: signal transduction pathways, cellular mechanisms and genetic control. 1284 97


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