Nicotine inhibits the production of inflammatory mediators in U937 cells through modulation of nuclear factor-kappaB activation.
Cigarette smoke is a major risk factor for lung cancer and respiratory infections. This increased susceptibility may result from cigarette smoke-induced impairment of the immune system. In this study, we evaluated the effect of nicotine on the production of inflammatory mediators by activated macrophages. Pretreatment with nicotine caused a significant inhibition of LPS-induced IL-1, IL-8, and PGE2 expression at the transcriptional level in U937 cells. Nicotine inhibited the activation of a transcription factor, NF-kappaB, which in turn, binds to and mediates transcriptional activation of these genes. These inhibitory effects of nicotine may contribute to cigarette smoke-induced immunosuppression.
Sugano
N
N
Department of Periodontology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8310, Japan. sugano-n@dent.nihon-u.ac.jp
Shimada
K
K
Ito
K
K
Murai
S
S
D051546:Cyclooxygenase 2; D016207:Cytokines / Q000235:genetics*; D015232:Dinoprostone / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007249:Inflammation; D007375:Interleukin-1 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008565:Membrane Proteins; D016328:NF-kappa B / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*; D020298:U937 Cells
D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D016328:NF-kappa B; D009538:Nicotine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone