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.
Wong
H R
HR
Divisions of Critical Care Medicine and Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, OH, 45229, USA. wonghr@chmcc.org
Ryan
M A
MA
Menendez
I Y
IY
Wispé
J R
JR
D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D006358:Hot Temperature; D006801:Humans; D020672:I-kappa B Proteins; D007249:Inflammation / Q000517:prevention & control; D008156:Luciferases / Q000235:genetics; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D008156:Luciferases