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Heat shock factor‐1 regulates IL‐6 promoter activity in C2C12 muscle myotubes
Author(s) -
Welc Steven S,
Chen Daniel L,
Judge Andrew R,
Clanton Thomas L
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1200.2
Subject(s) - microbiology and biotechnology , myogenesis , transfection , promoter , heat shock , chemistry , reporter gene , biology , heat shock protein , myocyte , gene , gene expression , biochemistry
Hyperthermia stimulates interleukin‐6 (IL‐6) mRNA and protein production and also potentiates the IL‐6 response to epinephrine (EPI) and lipopolysaccharide (LPS), but the signaling pathways are not known. In this study we specifically tested the role of heat shock factor‐1 (HSF‐1) in these responses using a mouse IL‐6 promoter reporter construct (mIL‐6.Luc) in C2C12 myotubes. IL‐6 promoter activity was inhibited by co‐transfection of dominant negative (d.n.) HSF‐1 or stimulated using a constitutively active (c.a.) HSF‐1 construct. The d.n. HSF‐1 significantly diminished IL‐6 promoter activity at both 37°C and 42°C (P < 0.05). Furthermore, the d.n. HSF‐1 significantly reduced the IL‐6 transcriptional responses to EPI (100 ng/ml) and LPS (1 ug/ml) at both 37°C and 42°C (P < 0.05). In contrast, co‐transfection with c.a. HSF‐1 significantly elevated IL‐6. Luc reporter activity at 37°C and amplified the response to LPS (P< 0.05); however, it had no influence on the response to EPI. Results demonstrate that hyperthermia is an important functional stimulus for IL‐6 promoter activity, which employs HSF‐1 activation. In addition, the interactions of overexpressed HSF‐1 with stress signals (from EPI or LPS) and the IL‐6 promoter have different regulatory outcomes. The overexpression of HSF‐1 does not amplify the IL‐6 promoter's response to EPI. The results confirm the important role of HSF‐1 in IL‐6 regulation and suggest that hyperthermia may also recruit other parallel signaling pathways besides HSF‐1 that influence IL‐6 regulation. Supported by: AHA #11GRNT7990119