title: 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.
abstract: 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.
authors.affiliation: Department of Microbiology & Immunology, University of Rochester Medical Center, Rochester, NY 14642, U.S.A.
authors.forename: Hajime
authors.initials: H
authors.lastname: Ishinaga
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Jono
authors.forename: Jae Hyang
authors.initials: JH
authors.lastname: Lim
authors.forename: Kensei
authors.initials: K
authors.lastname: Komatsu
authors.forename: Xiangbin
authors.initials: X
authors.lastname: Xu
authors.forename: Jiyun
authors.initials: J
authors.lastname: Lee
authors.forename: Chang-Hoon
authors.initials: CH
authors.lastname: Woo
authors.forename: Haidong
authors.initials: H
authors.lastname: Xu
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Feng
authors.forename: Lin-Feng
authors.initials: LF
authors.lastname: Chen
authors.forename: Chen
authors.initials: C
authors.lastname: Yan
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Li
mesh_terms: D000107:Acetylation / Q000187:drug effects; D045744:Cell Line, Tumor; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D016328:NF-kappa B; D051996:Transcription Factor RelA; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D017868:Cyclic AMP-Dependent Protein Kinases