1. Retinoid ameliorates experimental autoimmune myositis, with modulation of Th cell differentiation and antibody production in vivo.
- Author
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Ohyanagi N, Ishido M, Suzuki F, Kaneko K, Kubota T, Miyasaka N, and Nanki T
- Subjects
- Animals, Benzoates pharmacology, Disease Models, Animal, Immunoglobulin G metabolism, Interleukin-1beta metabolism, Male, Mice, Mice, Mutant Strains, Myosins immunology, Nervous System Autoimmune Disease, Experimental drug therapy, Retinoids therapeutic use, T-Lymphocytes, Helper-Inducer drug effects, T-Lymphocytes, Helper-Inducer metabolism, Tetrahydronaphthalenes pharmacology, Th1 Cells drug effects, Th1 Cells metabolism, Th1 Cells pathology, Th2 Cells drug effects, Th2 Cells metabolism, Th2 Cells pathology, Transcription Factor AP-1 metabolism, Tumor Necrosis Factor-alpha metabolism, Antibodies metabolism, Cell Differentiation drug effects, Nervous System Autoimmune Disease, Experimental immunology, Nervous System Autoimmune Disease, Experimental prevention & control, Retinoids pharmacology, T-Lymphocytes, Helper-Inducer pathology
- Abstract
Objective: Polymyositis and dermatomyositis are chronic inflammatory muscle diseases. Retinoids are compounds that bind to the retinoic acid binding site of retinoic acid receptors and have biologic activities similar to those of vitamin A. Recent studies indicate that retinoids promote Th2 differentiation and suppress Th1 and Th17 differentiation in vitro. The present study was undertaken to examine the effects of a synthetic retinoid, Am80, on experimental autoimmune myositis as well as on Th phenotype development and antibody production., Methods: Experimental autoimmune myositis was induced in SJL/J mice by immunization with rabbit myosin. Am80 was administered orally once daily. Its effects were evaluated by measurement of the numbers of infiltrating inflammatory cells, production of inflammatory cytokines in muscle, production of Th-specific cytokines by myosin-stimulated splenic T cells, and production of antimyosin antibodies in serum., Results: In mice with experimental autoimmune myositis, orally administered Am80 significantly reduced the number of infiltrating inflammatory cells and the expression of tumor necrosis factor alpha and interleukin-1beta (IL-1beta) in muscle. Moreover, Am80 increased production of interferon-gamma, IL-4, and IL-10, but not IL-17, by myosin-stimulated splenic T cells of mice with experimental autoimmune myositis, suggesting that it could enhance differentiation into Th1 and Th2, but not Th17, in vivo. Am80 also decreased serum levels of IgG2a and IgG2b antimyosin antibodies, but did not affect levels of IgG1 antimyosin antibodies. In addition, it suppressed chemokine expression and activator protein 1 activity in myoblasts in vitro., Conclusion: The synthetic retinoid Am80 has an inhibitory effect on experimental autoimmune myositis. It might regulate the development of Th phenotype and antibody production in vivo, in addition to its effects on cytokine and chemokine production.
- Published
- 2009
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