Synergistic induction of nuclear factor-κB by transforming growth factor-β and tumour necrosis factor-α is mediated by protein kinase A-dependent RelA acetylation

Hajime Ishinaga, Hirofumi Jono, Jae Hyang Lim, Kensei Komatsu, Xiangbin Xu, Jiyun Lee, Chang Hoon Woo, Haidong Xu, Xin Hua Feng, Lin Feng Chen, Chen Yan, Jian Dong Li

Research output: Contribution to journalArticle

Abstract

The TGF-β (transforming growth factor-β) pathway represents an important signalling pathway involved in regulating diverse biological processes, including cell proliferation, differentiation and inflammation. Despite the critical role for TGF-β in inflammatory responses, its role in regulating NF-κB (nuclear factor-κB)-dependent inflammatory responses still remains unknown. In the present study we show that TGF-β1 synergizes with proinflammatory cytokine TNF-α (tumour necrosis factor-α) to induce NF-κB activation and the resultant inflammatory response in vitro and in vivo. TGF-β1 synergistically enhances TNF-α-induced NF-κB DNA binding activity via induction of RelA acetylation. Moreover, synergistic enhancement of TNF-α-induced RelA acetylation and DNA-binding activity by TGF-β1 is mediated by PKA (protein kinase A). Thus the present study reveals a novel role for TGF-β in inflammatory responses and provides new insight into the regulation of NF-κB by TGF-β signalling.

Original languageEnglish (US)
Pages (from-to)583-591
Number of pages9
JournalBiochemical Journal
Volume417
Issue number2
DOIs
StatePublished - Jan 15 2009

Keywords

  • Inflammatory response
  • Nuclear factor-κB (NF-κB)
  • Protein kinase A (PKA)
  • RelA acetylation
  • Transforming growthfactor-β1 (TGF-β1)
  • Tumour necrosis factor-α (TNF-α)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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