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TGF-β induces p65 acetylation to enhance bacteria-induced NF-κB activation.
- Source :
-
EMBO Journal . 2/14/2007, Vol. 26 Issue 4, p1150-1162. 13p. - Publication Year :
- 2007
-
Abstract
- Transforming growth factor-β (TGF-β) family members are multifunctional growth factors involved in regulating diverse biological processes. Despite the critical role for TGF-β in regulating cell proliferation, differentiation, migration and development, its role in regulating NF-κB-dependent inflammatory response still remains unclear. Here, we show that TGF-β1 induces acetylation of NF-κB p65 subunit to synergistically enhance bacterium nontypeable Haemophilus influenzae-induced NF-κB activation and inflammatory response in vitro and in vivo. The TGF-β1-induced acetylation of p65 is mediated via a Smad3/4-PKA-p300-dependent signaling pathway. Acetylation of p65 at lysine 221 by TGF-β1 is critical for synergistic enhancement of bacteria-induced DNA-binding activity, NF-κB activation, NF-κB-dependent transcription of TNF-α and IL-1β and interstitial polymorphonuclear neutrophil infiltration in vitro and in vivo. These studies provide new insights into the novel regulation of NF-κB by TGF-β signaling. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02614189
- Volume :
- 26
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- EMBO Journal
- Publication Type :
- Academic Journal
- Accession number :
- 24099546
- Full Text :
- https://doi.org/10.1038/sj.emboj.7601546