Heat shock activates the I-kappaBalpha promoter and increases I-kappaBalpha mRNA expression.

Recent data indicate that the heat shock response inhibits nuclear translocation of the proinflammatory transcription factor NF-kappaB. Under basal conditions NF-kappaB is retained in the cytoplasm by an inhibitory protein called I-kappaB which exists as two major isoforms: I-kappaBalpha and I-kappaBbeta. Induction of the heat shock response in BEAS-2B cells, a human cell line representative of bronchial epithelium, increased expression of I-kappaBalpha mRNA in a time-dependent manner. Coincubation with actinomycin-D inhibited heat shock-mediated expression of I-kappaBalpha mRNA. Transient transfection assays with a plasmid containing the reporter gene firefly luciferase, under the control of the human I-kappaBalpha promoter, demonstrated that heat shock activated the I-kappaBalpha promoter. Heat shock-mediated induction of I-kappaBalpha was associated with inhibition of NF-kappaB activation. We conclude that heat shock increases I-kappaBalpha mRNA expression in BEAS-2B cells by activating the I-kappaBalpha promoter, and propose that heat shock-mediated up-regulation of I-kappaBalpha is a potential mechanism by which the heat shock response inhibits proinflammatory responses in lung cells.