Heat shock inhibits activation of NF-kappaB in the absence of heat shock factor-1.
The heat shock response is known to inhibit NF-kappaB activation and NF-kappaB-dependent gene expression. Herein we determined if cells lacking heat shock factor-1 (HSF-1), the major transcription factor regulating heat shock protein gene expression, have an altered ability to modulate NF-kappaB activation. Embryonic fibroblasts from HSF-1-null mutant mice (HSF-1-/- cells) had a drastically reduced ability to express heat shock protein-70 in response to heat shock, compared to embryonic fibroblasts from wild-type mice (HSF+/+ cells). There was no difference, however, in the ability of heat shock to inhibit TNFalpha-mediated NF-kappaB activation, IkappaBalpha degradation, IkappaB kinase activation, and macrophage chemotactic protein-1 expression in the HSF-1-/- cells compared to the HSF-1+/+ cells. These data demonstrate that heat shock inhibits activation of the NF-kappaB/IkappaBalpha pathway and NF-kappaB-dependent gene expression in the absence of an intact heat shock response.
Malhotra
Vivek
V
Division of Critical Care Medicine, Children's Hospital Medical Center and Children's Hospital Research Foundation, Cincinnati, Ohio 45229-3039, USA.
Eaves-Pyles
Tonyia
T
Odoms
Kelli
K
Quaid
Gina
G
Shanley
Thomas P
TP
Wong
Hector R
HR
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018932:Chemokine CCL2; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D017346:Protein Serine-Threonine Kinases; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse