title: TGF-beta induces p65 acetylation to enhance bacteria-induced NF-kappaB activation.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
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: Soo-Mi
authors.initials: SM
authors.lastname: Kweon
authors.forename: Haodong
authors.initials: H
authors.lastname: Xu
authors.forename: Un-Hwan
authors.initials: UH
authors.lastname: Ha
authors.forename: Haidong
authors.initials: H
authors.lastname: Xu
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Koga
authors.forename: Chen
authors.initials: C
authors.lastname: Yan
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Feng
authors.forename: Lin-Feng
authors.initials: LF
authors.lastname: Chen
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Li
mesh_terms: D000107:Acetylation; D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D006192:Haemophilus Infections / Q000378:metabolism*; D006193:Haemophilus influenzae; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008156:Luciferases; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D051900:Smad3 Protein / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D051900:Smad3 Protein; D051996:Transcription Factor RelA; D016212:Transforming Growth Factor beta; D008156:Luciferases