PMID- 8832978
OWN - NLM
STAT- MEDLINE
DCOM- 19970512
LR  - 20220227
IS  - 0315-162X (Print)
IS  - 0315-162X (Linking)
VI  - 23
IP  - 3
DP  - 1996 Mar
TI  - Antioxidants inhibit tumor necrosis factor-alpha mediated stimulation of 
      interleukin-8, monocyte chemoattractant protein-1, and collagenase expression in 
      cultured human synovial cells.
PG  - 432-8
AB  - OBJECTIVE: To study whether the induction of mRNA for interleukin-8 (IL-8), 
      monocyte chemoattractant protein-1 (MCP-1), and collagenase by tumor necrosis 
      factor-alpha (TNF-alpha) is suppressed by antioxidants in human synovial cells. 
      TNF-alpha has been shown to exert some of its effects by stimulating production 
      of reactive oxygen intermediates in some cell lines other than synovial cells. 
      METHODS: Amounts of mRNA for IL-8, MCP-1, and collagenase were determined by 
      Northern blot analysis. Electrophoretic mobility shift assays were performed for 
      the detection of a transcription factor, nuclear factor-kappa B(NF-kappa B). The 
      concentration of IL-8 in the medium was determined by ELISA. RESULTS: TNF-alpha 
      increased the expression of IL-8, MCP-1, and collagenase mRNA in human synovial 
      cells. NF-KB known to induce IL-8 gene transcription was also increased in 
      nuclear extracts from the synovial cells treated with TNF-alpha. Prior addition 
      of antioxidant, N-acetyl-L-cysteine (NAC) or 2-oxothiazolidine-4-carboxylate 
      (OTC), suppressed TNF-alpha stimulated expressions of IL-8, MCP-1, and 
      collagenase mRNA in a dose dependent manner. Treatment with NAC also suppressed 
      TNF-alpha induced increase in NF-kappa B. The changes of IL-8 in the medium 
      reflected the mRNA levels. Hydrogen peroxide (H2O2) induced the expression of 
      mRNA for the cytokines but not collagenase mRNA, and NAC suppressed the effect of 
      H2O2. CONCLUSION: Our data suggest that TNF-alpha induces expression of 
      proinflammatory cytokines such as IL-8 and MCP-1 through generation of reactive 
      oxygen intermediates and subsequent activation of NF-kappa B in human synovial 
      cells, and the antioxidants may inhibit, at least in part, the activation of 
      NF-kappa B by TNF-alpha. These results indicate that antioxidants such as NAC may 
      be useful in treating rheumatoid arthritis.
FAU - Sato, M
AU  - Sato M
AD  - Department of Endocrinology and Metabolism Research, Nagoya University, Furo-cho 
      Chikusa-ku, Japan.
FAU - Miyazaki, T
AU  - Miyazaki T
FAU - Nagaya, T
AU  - Nagaya T
FAU - Murata, Y
AU  - Murata Y
FAU - Ida, N
AU  - Ida N
FAU - Maeda, K
AU  - Maeda K
FAU - Seo, H
AU  - Seo H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Canada
TA  - J Rheumatol
JT  - The Journal of rheumatology
JID - 7501984
RN  - 0 (Antioxidants)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Interleukin-8)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Thiazoles)
RN  - 0 (Thiazolidines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 3.4.24.- (Collagenases)
RN  - SZB83O1W42 (Pyrrolidonecarboxylic Acid)
RN  - WYQ7N0BPYC (Acetylcysteine)
RN  - X7063P804E (2-oxothiazolidine-4-carboxylic acid)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Antioxidants/*pharmacology
MH  - Arthritis, Rheumatoid/drug therapy
MH  - Cells, Cultured/chemistry/drug effects/enzymology
MH  - Chemokine CCL2/*genetics
MH  - Collagenases/*genetics
MH  - Free Radical Scavengers/pharmacology
MH  - Gene Expression Regulation, Enzymologic/drug effects/immunology
MH  - Humans
MH  - Hydrogen Peroxide/metabolism
MH  - Interleukin-8/*genetics
MH  - NF-kappa B/genetics
MH  - Pyrrolidonecarboxylic Acid
MH  - RNA, Messenger/metabolism
MH  - Synovial Membrane/cytology
MH  - Thiazoles/pharmacology
MH  - Thiazolidines
MH  - Transcription, Genetic/drug effects
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1996/03/01 00:00
MHDA- 1996/03/01 00:01
CRDT- 1996/03/01 00:00
PHST- 1996/03/01 00:00 [pubmed]
PHST- 1996/03/01 00:01 [medline]
PHST- 1996/03/01 00:00 [entrez]
PST - ppublish
SO  - J Rheumatol. 1996 Mar;23(3):432-8.