Cigarette smoke condensate upregulates the gene and protein expression of proinflammatory cytokines in human fibroblast-like synoviocyte line.
Rheumatoid arthritis (RA) is characterized by proliferation of synoviocytes that produce proinflammatory cytokines, which are implicated in the pathogenesis of RA. When human fibroblast-like synoviocytes line MH7A was treated with cigarette smoke condensate (CSC), either mainstream or sidestream, expression levels of interleukin (IL)-1alpha, IL-1beta, IL-6, IL-8, and CYP1A1 mRNA were upregulated in both time- and dose-dependent manners. The upregulatory effects of CSC on these cytokines were not significantly inhibited by alpha-naphthoflavone, an aryl hydrocarbon receptor (AhR) antagonist, suggesting that the effects of CSC were independent of AhR. Cycloheximide treatment indicated that the augmenting effect of CSC on IL-1alpha, IL-1beta and IL-8, but not IL-6 and CYP1A1, mRNA expression requires de novo protein synthesis. CSC also induced cytokines at protein levels and further augmented the effects of tumor necrosis factor alpha on induction of these cytokines at both mRNA and protein levels. These results support the epidemiological studies indicating a strong association between heavy cigarette smoking and pathogenesis of RA.
Shizu
Miki
M
Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho, Nagoya, Japan.
Itoh
Yuka
Y
Sunahara
Ryohei
R
Chujo
Satomi
S
Hayashi
Hidetoshi
H
Ide
Yuko
Y
Takii
Takemasa
T
Koshiko
Masaya
M
Chung
Sang Woon
SW
Hayakawa
Kazuichi
K
Miyazawa
Keiji
K
Hirose
Kunitaka
K
Onozaki
Kikuo
K
D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D001571:Benzoflavones / Q000494:pharmacology; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism* / Q000473:pathology; D013582:Synovial Fluid / Q000378:metabolism*; D013997:Time Factors; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D015854:Up-Regulation / Q000187:drug effects*
D001571:Benzoflavones; D016207:Cytokines; D018836:Inflammation Mediators; D011500:Protein Synthesis Inhibitors; D018336:Receptors, Aryl Hydrocarbon; D014028:Tobacco Smoke Pollution; C011512:alpha-naphthoflavone; D003513:Cycloheximide; D019363:Cytochrome P-450 CYP1A1