TGF-β induces p65 acetylation to enhance bacteria-induced NF-κB activation
TGF-β induces p65 acetylation to enhance bacteria-induced NF-κB activation
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DOI：
10.1038/sj.emboj.7601546
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发表时间：
2007-02-21
期刊：
影响因子：
11.4
通讯作者：
Li, Jian-Dong
中科院分区：
文献类型：
--
作者：
Ishinaga, Hajime;Jono, Hirofumi;Li, Jian-Dong
转化生长因子-β家族成员是一类多功能生长因子，参与调节多种生物过程。尽管转化生长因子-β在调节细胞增殖、分化、迁移和发育中起着关键作用，但它在调节依赖于核因子-kappaB的炎症反应中的作用仍不清楚。在这里，我们证明了转化生长因子-β1诱导核因子-kappa B p65亚基的乙酰化，协同增强细菌非分型流感嗜血杆菌诱导的核因子-kappaB的激活和体内的炎症反应。转化生长因子-β1诱导的p65乙酰化是通过Smad3/4-PKA-p300依赖的信号通路介导的。转化生长因子-β1对p65的乙酰化在细菌诱导的DNA结合活性、核因子-kappaB的激活、依赖于核因子-kappaB的肿瘤坏死因子-β和白介素1-β的转录以及间质中性粒细胞在体内外的浸润中起着至关重要的作用。这些研究为研究转化生长因子-β信号对核因子-kappaB的新调控提供了新的见解。
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-kappa B-dependent inflammatory response still remains unclear. Here, we show that TGF-beta 1 induces acetylation of NF-kappa B p65 subunit to synergistically enhance bacterium non-typeable Haemophilus influenzae-induced NF-kappa B activation and inflammatory response in vitro and in vivo. The TGF-beta 1-induced acetylation of p65 is mediated via a Smad3/4-PKA-p300-dependent signaling pathway. Acetylation of p65 at lysine 221 by TGF-b1 is critical for synergistic enhancement of bacteria-induced DNA-binding activity, NF-kappa B activation, NF-kappa B-dependent transcription of TNF-beta and IL-1 beta and interstitial polymorphonuclear neutrophil infiltration in vitro and in vivo. These studies provide new insights into the novel regulation of NF-kappa B by TGF-beta signaling.