Tocopheryl Phosphate Inhibits Rheumatoid Arthritis-Related Gene Expression In Vitro and Ameliorates Arthritic Symptoms in Mice |
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| Authors: | Susumu Hama Naoko Kirimura Aki Obara Hirokatsu Takatsu Kentaro Kogure |
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| Institution: | 1.Faculty of Pharmacy, Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo 202-8585, Japan;2.Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan;3.Department of Analytical Chemistry, Kyorin University, Tokyo 181-8612, Japan; (A.O.); (H.T.);4.Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770-8505, Japan |
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| Abstract: | Anti-rheumatoid arthritis (RA) effects of α-tocopherol (α-T) have been shown in human patients in a double-blind trial. However, the effects of α-T and its derivatives on fibroblast-like synoviocytes (FLS) during the pathogenesis of RA remain unclear. In the present study, we compared the expression levels of genes related to RA progression in FLS treated with α-T, succinic ester of α-T (TS), and phosphate ester of α-T (TP), as determined via RT-PCR. The mRNA levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), matrix metalloproteinase (MMP)-3, and MMP-13 were reduced by treatment with TP without cytotoxicity, while α-T and TS did not show such effects. Furthermore, intraperitoneal injection of TP ameliorated the edema of the foot and joint and improved the arthritis score in laminarin-induced RA model mice. Therefore, TP exerted anti-RA effects through by inhibiting RA-related gene expression. |
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| Keywords: | α -tocopherol tocopheryl phosphate tocopheryl succinate rheumatoid arthritis |
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