The anti-allergic compound tranilast attenuates inflammation and inhibits bone destruction in collagen-induced arthritis in mice
| Autor: | Shiota N., Kovanen P. T., Eklund K. K., Shibata N., Shimoura K., Niibayashi T., Shimbori C., Okunishi H. |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Oligonucleotides Osteoclasts Bone and Bones Arthritis Rheumatoid Mice Anti-Allergic Agents Animals ortho-Aminobenzoates Mast Cells cathepsin-K chymase mat cell osteoclast RANK RANKL SCF TNF-alpha tryptase Inflammation Stem Cell Factor Receptor Activator of Nuclear Factor-kappa B Interleukin-6 Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha X-Rays RANK Ligand Synovial Membrane Arthritis Experimental Research Papers Interleukin-10 Cartilage Mice Inbred DBA Carrier Proteins |
| Zdroj: | British journal of pharmacology. 159(3) |
| ISSN: | 1476-5381 |
| Popis: | Recent findings suggest the importance of mast cells in the pathogenesis of rheumatoid arthritis and their potential as a therapeutic target. Tranilast is an anti-allergic compound with a potent membrane-stabilizing effect on mast cells and a wide range of anti-inflammatory effects, thus may be advantageous in the treatment of arthritis. Here, we have evaluated the effects of tranilast on the progression of collagen-induced arthritis in mice.Tranilast (400 mg.kg(-1).day(-1)) was orally administered for 8 weeks to mice with established collagen-induced arthritis. Arthritis was assessed by clinical signs and X-ray scores. In paw tissue, the numbers of mast cells and osteoclasts were measured by histological analysis, and several inflammatory factors were assessed by RT-PCR and Western blot analysis.*TNF-alpha-positive mast cells were present extensively throughout the inflamed synovium of vehicle-treated arthritic mice, with some mast cells in close proximity to osteoclasts in areas of marked bone and cartilage destruction. Tranilast significantly reduced clinical and X-ray scores of arthritis and decreased numbers of TNF-alpha-positive mast cells and mRNA levels of TNF-alpha, chymase (mouse mast cell protease 4), tryptase (mouse mast cell protease 6), stem cell factor, interleukin-6, cathepsin-K, receptor activator of nuclear factor-kappaB, and of receptor activator of nuclear factor-kappaB-ligand, but increased interleukin-10 mRNA level in paws of arthritic mice. Osteoclast numbers were decreased by treatment with tranilast.Tranilast possesses significant anti-rheumatic efficacy and, probably, this therapeutic effect is partly mediated by inhibition of mast cell activation and osteoclastogenesis. |
| Databáze: | OpenAIRE |
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