論文

査読有り
2006年10月

Infliximab neutralizes the suppressive effect of TNF-alpha on expression of extracellular-superoxide dismutase in vitro

BIOLOGICAL & PHARMACEUTICAL BULLETIN
  • Tetsuo Adachi
  • ,
  • Taisuke Toishi
  • ,
  • Eiji Takashima
  • ,
  • Hirokazu Hara

29
10
開始ページ
2095
終了ページ
2098
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1248/bpb.29.2095
出版者・発行元
PHARMACEUTICAL SOC JAPAN

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 11 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-a (TNF-alpha) has been implicated in the pathological conditions of the above diseases and is a major therapeutic target, based on clinical studies with anti-TNF-alpha monoclonal antibodies such as infliximab. In this report, we investigated the effect of TNF-alpha 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-alpha. Simultaneous addition of infliximab dose-dependently and significantly prevented the suppressive effects of TNF-alpha. p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, prevented significantly the suppressive effect of TNF-alpha suggesting that p38 MAPK is an important signaling molecule downstream of TNF-alpha to inhibit the EC-SOD expression. From the results, it is speculated that the decline in TNF-alpha 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-alpha related pathological conditions such as arthritis and insulin resistance.

Web of Science ® 被引用回数 : 21

リンク情報
DOI
https://doi.org/10.1248/bpb.29.2095
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/17015957
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000241546600020&DestApp=WOS_CPL