Synergistic induction of nuclear factor-kappaB by transforming growth factor-beta and tumour necrosis factor-alpha is mediated by protein kinase A-dependent RelA acetylation.


Journal Article

The TGF-beta (transforming growth factor-beta) pathway represents an important signalling pathway involved in regulating diverse biological processes, including cell proliferation, differentiation and inflammation. Despite the critical role for TGF-beta in inflammatory responses, its role in regulating NF-kappaB (nuclear factor-kappaB)-dependent inflammatory responses still remains unknown. In the present study we show that TGF-beta1 synergizes with proinflammatory cytokine TNF-alpha (tumour necrosis factor-alpha) to induce NF-kappaB activation and the resultant inflammatory response in vitro and in vivo. TGF-beta1 synergistically enhances TNF-alpha-induced NF-kappaB DNA binding activity via induction of RelA acetylation. Moreover, synergistic enhancement of TNF-alpha-induced RelA acetylation and DNA-binding activity by TGF-beta1 is mediated by PKA (protein kinase A). Thus the present study reveals a novel role for TGF-beta in inflammatory responses and provides new insight into the regulation of NF-kappaB by TGF-beta signalling.

Full Text

Cited Authors

  • Ishinaga, H; Jono, H; Lim, JH; Komatsu, K; Xu, X; Lee, J; Woo, C-H; Xu, H; Feng, X-H; Chen, L-F; Yan, C; Li, J-D

Published Date

  • January 2009

Published In

Volume / Issue

  • 417 / 2

Start / End Page

  • 583 - 591

PubMed ID

  • 18823280

Pubmed Central ID

  • 18823280

Electronic International Standard Serial Number (EISSN)

  • 1470-8728

International Standard Serial Number (ISSN)

  • 0264-6021

Digital Object Identifier (DOI)

  • 10.1042/bj20080781


  • eng