title: Induction of interleukin-6 expression by bone morphogenetic protein-6 in macrophages requires both SMAD and p38 signaling pathways.
abstract: Unlike the prototype transforming growth factor-β (TGF-β), bone morphogenetic protein-6 (BMP-6) activates macrophages. Here, we report that BMP-6 induces the expression of IL-6 in macrophages. Using overexpression and knockdown experiments, we demonstrate that BMP receptor type II and activin-like kinase-2 are necessary for IL-6 induction by BMP-6. At the intracellular level, both Smad and p38 signaling pathways are required for the induction of IL-6. The cross-talk between the two pathways occurs at the level of transcription factor GATA4 and Smad 1/4. These results, taken together, demonstrate a novel BMP-6 signaling mechanism in which both the Smad and non-Smad pathways directly interact to activate the transcription of a target gene.
authors.affiliation: Dean and Betty Gallo Prostate Cancer Center and Section of Urologic Oncology, Division of Urology, Department of Surgery, the Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, USA.
authors.forename: Geun Taek
authors.initials: GT
authors.lastname: Lee
authors.forename: Seok Joo
authors.initials: SJ
authors.lastname: Kwon
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Seong Soo
authors.initials: SS
authors.lastname: Jeon
authors.forename: Kee Taek
authors.initials: KT
authors.lastname: Jang
authors.forename: Han Yong
authors.initials: HY
authors.lastname: Choi
authors.forename: Hyun Moo
authors.initials: HM
authors.lastname: Lee
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.forename: Seong Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Isaac Yi
authors.initials: IY
authors.lastname: Kim
mesh_terms: D030201:Activin Receptors, Type I / Q000378:metabolism; D000818:Animals; D055418:Bone Morphogenetic Protein 6 / Q000378:metabolism*; D002460:Cell Line; D050991:GATA4 Transcription Factor / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D015398:Signal Transduction; D051898:Smad1 Protein / Q000378:metabolism; D051901:Smad4 Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D055418:Bone Morphogenetic Protein 6; D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D015850:Interleukin-6; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases; D030201:Activin Receptors, Type I; C498943:Acvr1 protein, mouse