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*

*この研究の対応する著者

研究成果: Article査読

49 被引用数 (Scopus)

抄録

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.

本文言語English
ジャーナルAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
264
1 27-1
出版ステータスPublished - 1993
外部発表はい

ASJC Scopus subject areas

  • 生理学
  • 消化器病学

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