De-repression of heat shock transcription factor-1 in interleukin-6- treated hepatocytes is mediated by downregulation of glycogen synthase kinase 3β and MAPK/ERK-1

  • Authors:
    • Stephen J. Wigmore
    • Kathryn Sangster
    • Stephen J. McNally
    • Ewen M. Harrison
    • James A. Ross
    • Kenneth C.H. Fearon
    • O. James Garden
  • View Affiliations

  • Published online on: March 1, 2007     https://doi.org/10.3892/ijmm.19.3.413
  • Pages: 413-420
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Abstract

Expression of inducible heat shock protein (HSP70) requires activation of heat shock transcription factor-1 (HSF-1). Recent evidence suggests that interleukin-6 (IL-6) can modify the response of HSF-1 to heat. We hypothesized that IL-6 would prime the HSP response by causing de-repression of HSF-1 resulting in augmented HSP expression in stressed cells. In this study we show that IL-6 has no direct effect on HSP70 expression at 37°C but does augment HSP70 expression in response to heat. IL-6 treatment decreased active MAPK/pERK and glycogen synthase kinase 3β (GSK3β) expression and GSK3β kinase activity. In IL-6-treated cells, monomeric HSF-1 accumulated in the cytoplasm and nucleus, bound DNA but was transcriptionally inactive. On exposure to heat shock this modified monomer assumed the transcriptionally active phenotype with trimerization and hyperphosphorylation evident. The increased induction of HSP70 in IL-6 and heat-treated cells was inhibited using PI3-kinase inhibitors or Akt inhibition and was HSF-1 dependent. IL-6, via the PI3-kinase/Akt pathway leads to inhibition of the repressive kinases MAPK/pERK and GSK3β, and this converts inactive HSF-1 to an intermediate DNA-binding form augmenting transcriptional activation in the presence of a second stressor.

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March 2007
Volume 19 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Wigmore SJ, Sangster K, McNally SJ, Harrison EM, Ross JA, Fearon KC and Garden OJ: De-repression of heat shock transcription factor-1 in interleukin-6- treated hepatocytes is mediated by downregulation of glycogen synthase kinase 3β and MAPK/ERK-1. Int J Mol Med 19: 413-420, 2007
APA
Wigmore, S.J., Sangster, K., McNally, S.J., Harrison, E.M., Ross, J.A., Fearon, K.C., & Garden, O.J. (2007). De-repression of heat shock transcription factor-1 in interleukin-6- treated hepatocytes is mediated by downregulation of glycogen synthase kinase 3β and MAPK/ERK-1. International Journal of Molecular Medicine, 19, 413-420. https://doi.org/10.3892/ijmm.19.3.413
MLA
Wigmore, S. J., Sangster, K., McNally, S. J., Harrison, E. M., Ross, J. A., Fearon, K. C., Garden, O. J."De-repression of heat shock transcription factor-1 in interleukin-6- treated hepatocytes is mediated by downregulation of glycogen synthase kinase 3β and MAPK/ERK-1". International Journal of Molecular Medicine 19.3 (2007): 413-420.
Chicago
Wigmore, S. J., Sangster, K., McNally, S. J., Harrison, E. M., Ross, J. A., Fearon, K. C., Garden, O. J."De-repression of heat shock transcription factor-1 in interleukin-6- treated hepatocytes is mediated by downregulation of glycogen synthase kinase 3β and MAPK/ERK-1". International Journal of Molecular Medicine 19, no. 3 (2007): 413-420. https://doi.org/10.3892/ijmm.19.3.413