Medical College of Wisconsin
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Febrile-range temperature modifies cytokine gene expression in LPS-stimulated macrophages by differentially modifying NF-{kappa}B recruitment to cytokine gene promoters. Am J Physiol Cell Physiol 2010 Jan;298(1):C171-81

Date

10/23/2009

Pubmed ID

19846753

Pubmed Central ID

PMC2806152

DOI

10.1152/ajpcell.00346.2009

Scopus ID

2-s2.0-73549123428   32 Citations

Abstract

We previously showed that exposure to febrile-range temperatures (FRT, 39.5-40 degrees C) reduces LPS-induced TNF-alpha expression, in part through the direct interaction of heat shock factor-1 (HSF1) with the TNF-alpha gene promoter. However, it is not known whether exposure to FRT also modifies more proximal LPS-induced signaling events. Using HSF1-null mice, we confirmed that HSF1 is required for FRT-induced repression of TNF-alpha in vitro by LPS-stimulated bone marrow-derived macrophages and in vivo in mice challenged intratracheally with LPS. Exposing LPS-stimulated RAW 264.7 mouse macrophages to FRT reduced TNF-alpha expression while increasing IL-1beta expression despite the two genes sharing a common myeloid differentiation protein-88 (MyD88)-dependent pathway. Global activation of the three LPS-induced signaling intermediates that lead to cytokine gene expression, ERK and p38 MAPKs and NF-kappaB, was not affected by exposing RAW 264.7 cells to FRT as assessed by ERK and p38 phosphorylation and NF-kappaB in vitro DNA-binding activity and activation of a NF-kappaB-dependent synthetic promoter. However, chromatin immunoprecipitation (ChIP) analysis demonstrated that exposure to FRT reduced LPS-induced recruitment of NF-kappaB p65 to the TNF-alpha promoter while simultaneously increasing its recruitment to the IL-1beta promoter. These data suggest that FRT exerts its effects on cytokine gene expression in a gene-specific manner through distal effects on promoter activation rather than proximal receptor activation and signal transduction.

Author List

Cooper ZA, Ghosh A, Gupta A, Maity T, Benjamin IJ, Vogel SN, Hasday JD, Singh IS

Author

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

Animals
Chromatin
Crosses, Genetic
Cytokines
DNA
DNA-Binding Proteins
Female
Fever
Gene Expression Regulation
Heat Shock Transcription Factors
Interleukin-1beta
Lipopolysaccharides
Macrophages
Male
Mice
Mice, Knockout
NF-kappa B
Polymerase Chain Reaction
Promoter Regions, Genetic
RNA
Temperature
Transcription Factors
Tumor Necrosis Factor-alpha
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a