Regular ArticleTobacco Smoke Induces Coordinate Activation of HSF and Inhibition of NFκB in Human Monocytes: Effects on TNFα 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)α. 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 NFκB. Thus, we also determined the effects of TS on NFκB. U937 cells and human peripheral blood monocytes were exposed to TS, binding activities of the respective transcription factors were analyzed, and Hsp70 expression and TNFα release were determined in parallel. TS activated HSF, which was associated with Hsp70 overexpression and inhibition of NFκB binding activity and TNFα release. The altered cytokine profile observed in smokers may relate to an HSF/Hsp70-mediated inhibition of NFκB activity.