Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 548, Issue 1-3, Pages 158-166Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2006.07.046
Keywords
arthritis; cysteinyl leukotriene; mast cell; TNF-alpha
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Our previous study showed that the number of mast cells was increased in the inflamed paws of collagen-induced arthritis in mice, and treatment with a mast cell-stabilizing compound effectively suppressed the development of collagen-induced arthritis. A recent in vitro study showed that mast cells express cysteinyl leukotriene type I receptor, and that a cysteinyl leukotriene type I receptor antagonist inhibits the production of TNF-alpha by mast cells. To further investigate the role of mast cells in vivo, we evaluated the therapeutic effects of a cysteinyl leukotriene type I receptor antagonist, montelukast, on the development of collagen-induced arthritis in mice. Montelukast (10 mg/kg/day) or vehicle was orally administered to mice for 12 weeks, starting 6 weeks after immunization with bovine type 11 collagen. Treatment with montelukast significantly reduced clinical scores and X-ray scores of collagen-induced arthritis, and decreased the number of mast cells in the inflamed paws of collagen-induced arthritic mice. Immunohistochemical analysis revealed that mast cells in the inflamed synovium were one of the major cells producing TNF-alpha and that the number of TNF-a positive mast cells was significantly reduced by treatment with montelukast. Furthermore, TNF-alpha and SCF mRNA levels in the paws of collagen-induced arthritic mice were markedly decreased by montelukast treatment. Montelukast may lead to a beneficial therapeutic effect by inhibiting TNF-alpha production by mast cells. (c) 2006 Elsevier B.V. All rights reserved.
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