1. TGF-β induces p65 acetylation to enhance bacteria-induced NF-κB activation.
- Author
-
Hajime Ishinaga, Hirofumi Jono, Jae Hyang Lim, Soo-Mi Kweon, Haodong Xu, Un-Hwan Ha, Haidong Xu, Tomoaki Koga, Chen Yan, Feng, Xin-Hua, Lin-Feng Chen, and Jian-Dong Li
- Subjects
ACETYLATION ,BACTERIA ,TRANSFORMING growth factors ,CELL proliferation ,HAEMOPHILUS influenzae - 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]
- Published
- 2007
- Full Text
- View/download PDF