Polycyclic aromatic hydrocarbon increases mRNA level for interleukin 1 beta in human fibroblast-like synoviocyte line via aryl hydrocarbon receptor.
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.
Tamaki
Ayako
A
Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho, Nagoya, Japan.
Hayashi
Hidetoshi
H
Nakajima
Hironori
H
Takii
Takemasa
T
Katagiri
Daichi
D
Miyazawa
Keiji
K
Hirose
Kunitaka
K
Onozaki
Kikuo
K
D001551:Benz(a)Anthracenes / Q000633:toxicity; D001564:Benzo(a)pyrene / Q000633:toxicity; D002460:Cell Line; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D008748:Methylcholanthrene; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D013582:Synovial Fluid / Q000166:cytology / Q000378:metabolism*; D015854:Up-Regulation
D001551:Benz(a)Anthracenes; D007375:Interleukin-1; D000072317:Polychlorinated Dibenzodioxins; D011084:Polycyclic Aromatic Hydrocarbons; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; D019363:Cytochrome P-450 CYP1A1