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Heat shock co-activates interleukin-8 transcription. Am J Respir Cell Mol Biol 2008 Aug;39(2):235-42



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Pubmed Central ID




Scopus ID

2-s2.0-48649092274   37 Citations


The heat shock (HS) response is a phylogenetically ancient cellular response to stress, including heat, that shifts gene expression to a set of conserved HS protein (HSP) genes. In our earlier studies, febrile-range hyperthermia (FRH) not only activated HSP gene expression, but also increased expression of CXC chemokines in mice, leading us to hypothesize that the CXC chemokine family of genes might be HS-responsive. To address this hypothesis we analyzed the effect of HS on the expression of IL-8/CXCL-8, a member of the human CXC family of ELR(+) chemokines. HS markedly enhanced TNF-alpha-induced IL-8 secretion in human A549 respiratory epithelial-like cells and in primary human small airway epithelial cells. IL-8 mRNA was also up-regulated by HS, but the stability of IL-8 mRNA was not affected. TNF-alpha-induced reporter activity of an IL-8 promoter construct IL8(-1471/+44)-luc stably transfected in A549 cells was also enhanced by HS. Electrophoretic mobility and chromatin immunoprecipitation assays showed that the stress-activated transcription factor heat shock factor-1 (HSF-1) binds to at least two putative heat shock response elements (HSE) present in the IL-8 promoter. Deletional reporter constructs lacking either one or both of these sites showed reduced HS responsiveness. Furthermore, depletion of HSF-1 using siRNA also reduced the effects HS on TNF-alpha-induced IL-8 expression, demonstrating that HSF-1 could also act to regulate IL-8 gene transcription. We speculate that during evolution the CXC chemokine genes may have co-opted elements of the HS response to amplify their expression and enhance neutrophil delivery during febrile illnesses.

Author List

Singh IS, Gupta A, Nagarsekar A, Cooper Z, Manka C, Hester L, Benjamin IJ, He JR, Hasday JD


Ivor J. Benjamin MD Center Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cell Line
DNA-Binding Proteins
Heat Shock Transcription Factors
Heat-Shock Proteins
Heat-Shock Response
Mice, Knockout
Transcription Factors
Transcriptional Activation
Tumor Necrosis Factor-alpha
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a