Tobacco smoke induces coordinate activation of HSF and inhibition of NFkappaB in human monocytes: effects on TNFalpha release.
Tobacco smoke (TS) exposure is a major risk factor for human disease, and macrophages of healthy smokers have a depressed capacity to release cytokines, including tumor necrosis factor (TNF)alpha. TS induces the synthesis of heat shock (HS)/stress proteins (HSP), and, in particular, of Hsp70. We determined whether Hsp70 induction by TS was mediated by the activation of the HS transcription factor, HSF. HSF activation has been shown to inhibit NFkappaB. Thus, we also determined the effects of TS on NFkappaB. U937 cells and human peripheral blood monocytes were exposed to TS, binding activities of the respective transcription factors were analyzed, and Hsp70 expression and TNFalpha release were determined in parallel. TS activated HSF, which was associated with Hsp70 overexpression and inhibition of NFkappaB binding activity and TNFalpha release. The altered cytokine profile observed in smokers may relate to an HSF/Hsp70-mediated inhibition of NFkappaB activity.
Vayssier
M
M
Laboratoire de Physiologie Respiratoire, UFR Cochin Port-Royal, 24 rue du Faubourg Saint-Jacques, Paris, 75014, France.
Favatier
F
F
Pinot
F
F
Bachelet
M
M
Polla
B S
BS
D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000097:blood; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000097:blood; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000097:blood; D006358:Hot Temperature; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008954:Models, Biological; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D014028:Tobacco Smoke Pollution; D014157:Transcription Factors / Q000096:biosynthesis / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D020298:U937 Cells
D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014028:Tobacco Smoke Pollution; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha