TGF-beta induces p65 acetylation to enhance bacteria-induced NF-kappaB activation.

Published

Journal Article

Transforming growth factor-beta (TGF-beta) family members are multifunctional growth factors involved in regulating diverse biological processes. Despite the critical role for TGF-beta in regulating cell proliferation, differentiation, migration and development, its role in regulating NF-kappaB-dependent inflammatory response still remains unclear. Here, we show that TGF-beta1 induces acetylation of NF-kappaB p65 subunit to synergistically enhance bacterium nontypeable Haemophilus influenzae-induced NF-kappaB activation and inflammatory response in vitro and in vivo. The TGF-beta1-induced acetylation of p65 is mediated via a Smad3/4-PKA-p300-dependent signaling pathway. Acetylation of p65 at lysine 221 by TGF-beta1 is critical for synergistic enhancement of bacteria-induced DNA-binding activity, NF-kappaB activation, NF-kappaB-dependent transcription of TNF-alpha and IL-1beta and interstitial polymorphonuclear neutrophil infiltration in vitro and in vivo. These studies provide new insights into the novel regulation of NF-kappaB by TGF-beta signaling.

Full Text

Cited Authors

  • Ishinaga, H; Jono, H; Lim, JH; Kweon, S-M; Xu, H; Ha, U-H; Xu, H; Koga, T; Yan, C; Feng, X-H; Chen, L-F; Li, J-D

Published Date

  • February 2007

Published In

Volume / Issue

  • 26 / 4

Start / End Page

  • 1150 - 1162

PubMed ID

  • 17268554

Pubmed Central ID

  • 17268554

Electronic International Standard Serial Number (EISSN)

  • 1460-2075

International Standard Serial Number (ISSN)

  • 0261-4189

Digital Object Identifier (DOI)

  • 10.1038/sj.emboj.7601546

Language

  • eng