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