Polycyclic Aromatic Hydrocarbon Increases mRNA Level for Interleukin 1 Beta in Human Fibroblast-Like Synoviocyte Line via Aryl Hydrocarbon Receptor (Analytical Biochemistry)

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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-1β 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 α-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-1β 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.
公益社団法人日本薬学会の論文
2004-03-01