PMID- 17015957
OWN - NLM
STAT- MEDLINE
DCOM- 20061129
LR  - 20190720
IS  - 0918-6158 (Print)
IS  - 0918-6158 (Linking)
VI  - 29
IP  - 10
DP  - 2006 Oct
TI  - Infliximab neutralizes the suppressive effect of TNF-alpha on expression of 
      extracellular-superoxide dismutase in vitro.
PG  - 2095-8
AB  - 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-alpha (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.
FAU - Adachi, Tetsuo
AU  - Adachi T
AD  - Department of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu, 
      Japan. adachi@gifu-pu.ac.jp
FAU - Toishi, Taisuke
AU  - Toishi T
FAU - Takashima, Eiji
AU  - Takashima E
FAU - Hara, Hirokazu
AU  - Hara H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - B72HH48FLU (Infliximab)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Antibodies, Monoclonal/*pharmacology
MH  - Cells, Cultured
MH  - Humans
MH  - Infliximab
MH  - RNA, Messenger/analysis
MH  - Superoxide Dismutase/*genetics
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors
MH  - p38 Mitogen-Activated Protein Kinases/physiology
EDAT- 2006/10/04 09:00
MHDA- 2006/12/09 09:00
CRDT- 2006/10/04 09:00
PHST- 2006/10/04 09:00 [pubmed]
PHST- 2006/12/09 09:00 [medline]
PHST- 2006/10/04 09:00 [entrez]
AID - JST.JSTAGE/bpb/29.2095 [pii]
AID - 10.1248/bpb.29.2095 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2006 Oct;29(10):2095-8. doi: 10.1248/bpb.29.2095.