Document Detail

Induction of cytokines and ICAM-1 by proinflammatory cytokines in primary rheumatoid synovial fibroblasts and inhibition by N-acetyl-L-cysteine and aspirin.
MedLine Citation:
PMID:  8921427     Owner:  NLM     Status:  MEDLINE    
The role of transcription factor NF-kappa B in the induction of cytokines and ICAM-1 upon stimulation with proinflammatory cytokines, IL-1 and tumor necrosis factor (TNF)-alpha was investigated in primary synovial fibroblasts obtained from patients with rheumatoid arthritis (RA). Nuclear translocation of NF-kappa B was demonstrated after 30 min of treatment with IL-1 or TNF-alpha. Thereafter, the production of several cytokines including granulocyte macrophage colony stimulating factor, IL-6 and IL-8, that are known to be abundantly produced in the synovial cavity of RA patients, was greatly augmented. Similarly, cell surface expression of ICAM-1 was induced by the IL-1 or TNF-alpha treatment. Since expression of these genes is induced in rheumatoid synovial tissue, this experimental system is considered to represent the in vivo situation of RA pathophysiology. Using this cell culture system we attempted to modulate the intracellular signaling cascade for NF-kappa B activation and examined the effects of N-acetyl-L-cysteine (NAC) and acetylsalicylic acid (aspirin), which were previously reported to inhibit NF-kappa B activation. Pretreatment of the primary synovial fibroblasts with NAC inhibited nuclear translocation of NF-kappa B. Subsequently, the induction of these cytokines and ICAM-1 was considerably suppressed. On the other hand, pretreatment with aspirin blocked these phenomena only partially. These observations indicate the pivotal role of NF-kappa B in RA pathogenesis thus highlighting the possibility of a novel therapeutic strategy.
S Sakurada; T Kato; T Okamoto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International immunology     Volume:  8     ISSN:  0953-8178     ISO Abbreviation:  Int. Immunol.     Publication Date:  1996 Oct 
Date Detail:
Created Date:  1997-02-10     Completed Date:  1997-02-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8916182     Medline TA:  Int Immunol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1483-93     Citation Subset:  IM    
Department of Molecular Genetics, Nagoya City University Medical School, Japan.
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MeSH Terms
Acetylcysteine / pharmacology*
Arthritis, Rheumatoid / drug therapy,  metabolism*
Aspirin / pharmacology*,  therapeutic use
Cells, Cultured
Cytokines / antagonists & inhibitors*,  biosynthesis*
Fibroblasts / metabolism*
Intercellular Adhesion Molecule-1 / biosynthesis*,  drug effects*
Interleukin-1 / antagonists & inhibitors,  pharmacology
NF-kappa B / antagonists & inhibitors*,  pharmacology*
Synovial Membrane / cytology,  metabolism*
Tumor Necrosis Factor-alpha / antagonists & inhibitors,  pharmacology
Reg. No./Substance:
0/Cytokines; 0/Interleukin-1; 0/NF-kappa B; 0/Tumor Necrosis Factor-alpha; 126547-89-5/Intercellular Adhesion Molecule-1; 50-78-2/Aspirin; 616-91-1/Acetylcysteine

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