NF-IL6 and HSF1 have mutually antagonistic effects on transcription in monocytic cells.
We have examined the functional antagonism between the regulator of the heat shock response, HSF1, and NF-IL6, which plays a major role in control of the acute phase response (APR). Agents that activate HSF1 such as heat shock and sodium salicylate inhibit NF-IL6 induced transcription while NF-IL6 activators such as lipopolysaccharide (LPS) and interleukin 6 (IL-6) repressed the stress responsive HSP70B promoter. In transfection studies, the inhibitory effects of HSF1 and NF-IL6 on the c-fms promoter were shown to be highly dose-dependent. Furthermore, heat shock is inhibitory to differentiation-linked expression of macrophage colony stimulating factor (M-CSF) receptor, product of the c-fms gene, which is transcriptionally activated by NF-IL6 but repressed by HSF1. Our studies suggest a strong mutual antagonism between the heat shock response and APR, which may influence the sensitivity and duration of inflammatory responses.
Xie
Yue
Y
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.
Chen
Changmin
C
Stevenson
Mary Ann
MA
Hume
David A
DA
Auron
Philip E
PE
Calderwood
Stuart K
SK
D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D016236:Genes, fms; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response; D015850:Interleukin-6 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011401:Promoter Regions, Genetic; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism; D020218:Response Elements; D012980:Sodium Salicylate / Q000494:pharmacology; D014157:Transcription Factors; D014158:Transcription, Genetic
D022782:CCAAT-Enhancer-Binding Protein-beta; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D018840:HSP70 Heat-Shock Proteins; C491129:HSPA7 protein, human; D000076249:Heat Shock Transcription Factors; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012097:Repressor Proteins; D014157:Transcription Factors; D016186:Receptor, Macrophage Colony-Stimulating Factor; D012980:Sodium Salicylate