文章基本信息

标题：Infliximab Neutralizes the Suppressive Effect of TNF-α on Expression of Extracellular-Superoxide Dismutase in Vitro
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作者：Tetsuo Adachi ; Taisuke Toishi ; Eiji Takashima 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2006
卷号：29
期号：10
页码：2095-2098
DOI：10.1248/bpb.29.2095
出版社：The Pharmaceutical Society of Japan
摘要：Extracellular-superoxide dismutase (EC-SOD) is the major SOD isozyme in blood vessel walls, normal cartilage and synovial fluid and may be important for the antioxidant capability of these tissues. We have reported that EC-SOD gene transferred mice exhibited significant suppression of clinical symptoms of type II collagen induced arthritis [Iyama, et al. , Arthritis Rheum. , 44, 2160—2167 (2001)] and plasma EC-SOD levels in type 2 diabetic patients were significantly negatively related to indices of insulin resistance [Adachi, et al. , J. Endocrinol. , 181, 413—417 (2004)]. Tumor necrosis factor-α (TNF-α) has been implicated in the pathological conditions of the above diseases and is a major therapeutic target, based on clinical studies with anti-TNF-α monoclonal antibodies such as infliximab. In this report, we investigated the effect of TNF-α on the expression of EC-SOD in cultured cells and the cooperating effect of infliximab. In the in vitro assays examined, expression of EC-SOD, but not other SOD isozymes, in smooth muscle and fibroblast cells were suppressed by the addition of TNF-α. Simultaneous addition of infliximab dose-dependently and significantly prevented the suppressive effects of TNF-α. p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, prevented significantly the suppressive effect of TNF-α suggesting that p38 MAPK is an important signaling molecule downstream of TNF-α to inhibit the EC-SOD expression. From the results, it is speculated that the decline in TNF-α activity by the administration of infliximab results in the liberation of EC-SOD from the suppressed state of gene expression. This reveals a potential usefulness of infliximab on TNF-α related pathological conditions such as arthritis and insulin resistance.
关键词：extracellular-superoxide dismutase;tumor necrosis factor-α;infliximab;mitogen-activated protein kinase;insulin resistance