Activation of activating protein 1 during hepatic acute phase response

Masahira Hattori, A. Tugores, J. K. Westwick, L. Veloz, H. L. Leffert, M. Karin, D. A. Brenner

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Abstract

During an acute phase response following inflammatory stimuli, specific changes occur in the synthesis and secretion of many hepatic proteins. Because the expression of differentiated function requires the coordinated regulation of many genes, we investigated the activity of general and tissue- specific transcription factors using a rat liver model of the acute phase response induced by Freund's adjuvant. Nuclear extracts and RNAs were prepared throughout a 48-h posttreatment period. Mobility shift assays revealed increased binding activity by nuclear factor-κB, interleukin-6 (IL- 6) responsive element binding protein, and activating protein 1 (AP-1). Two AP-1 complexes were induced during the acute phase response, and correlation between their presence and transcription activity was demonstrated by transfection studies. Elevated binding activity of AP-1 also correlated with elevated levels of c-jun, junD, junB, and c-fos mRNAs. Western blots showed elevated hepatic levels of c-Jun but not c-Fos proteins during the acute phase response. In addition, IL-6, tumor necrosis factor-α, and IL-1β, cytokine regulators of the acute phase response, stimulated expression of an AP-1 responsive reporter gene introduced by DNA-mediated transfection into adult rat hepatocytes in primary culture. These findings demonstrate the complexity of AP-1 hepatic transcription factor responses to humoral regulators with direct hepatocellular effects.

Original languageEnglish
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume264
Issue number1 27-1
Publication statusPublished - 1993
Externally publishedYes

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Keywords

  • c-Fos protein
  • c-Jun protein
  • interleukin- 1
  • interleukin-6
  • nuclear factor-κB
  • tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

Cite this

Hattori, M., Tugores, A., Westwick, J. K., Veloz, L., Leffert, H. L., Karin, M., & Brenner, D. A. (1993). Activation of activating protein 1 during hepatic acute phase response. American Journal of Physiology - Gastrointestinal and Liver Physiology, 264(1 27-1).