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Polycyclic aromatic hydrocarbon increases mRNA level for interleukin 1 beta in human fibroblast-like synoviocyte line
Ayako Tamaki1, Hidetoshi Hayashi, Hironori Nakajima
1Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho, Nagoya, Japan.
Abstract:
Rheumatoid arthritis (RA) is characterized by proliferation of synoviocytes that produce proinflammatory cytokines, which is implicated in the pathogenesis of the disease. Among the cytokines, IL-1 is the critical mediator of the disease. When human fibroblast-like synoviocytes line, MH7A, was treated with 3-methylcholanthrene (3-MC), a polycyclic aromatic hydrocarbon (PAH), mRNA of IL-1beta was up-regulated. MH7A cells express functional aryl hydrocarbon receptor (AhR) as shown by 3-MC-inducible CYP1A1 mRNA expression. The effect of 3-MC was inhibited by alpha-napthoflavone, an AhR antagonist, indicating that the effect of 3-MC is mediated via AhR. Benzo[a]pyrene (B[a]P) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) also up-regulated mRNA level of IL-1beta in the cells via AhR. As PAHs are much contained in cigarette smoke, these findings provide the possible basis for epidemiological studies indicating a strong association between heavy cigarette smoking and outcome of RA.
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