title: Effect of bone morphogenetic protein-6 on macrophages.
abstract: Bone morphogenetic proteins (BMPs) are members of the transforming growth factor (TGF)-beta superfamily which regulates bone formation, haematopoiesis and development. While TGF-beta is known to be a negative regulator of the immune system, the effect of BMPs on the immune system is largely unknown. Herein, the effect of BMP-6 on the innate immune system was investigated using the murine macrophage cell line RAW 264.7. BMP-6 altered cellular morphology, inhibited cellular proliferation, increased the fraction of subG(1) phase cells, and decreased the fraction of cells in the S and G(2)M phases, without changing the percentage of apoptotic cells. In addition, BMP-6 induced expression of pro-inflammatory inducible nitric oxide synthase (iNOS) and the cytokine tumour necrosis factor (TNF)-alpha. Reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated the expression of all three known type II BMP receptors [BMP-RII, activin (Act)-RIIA and Act-RIIB] and two of the three known type I receptors [activin receptor-like kinase 2 (ALK2) and ALK3]. Over-expression as well as knock-down studies using short hairpin RNA (shRNA) demonstrated that BMP-RII, ALK2 and ALK3 are the functional BMP-6 receptors in macrophages. Finally, the effect of BMP-6 was confirmed in murine peritoneal macrophages and the THP-1 human monocyte cell line. Taken together, these results demonstrate that BMP-6 regulates the proliferation and gene expression profile of macrophages.
authors.affiliation: Division of Urology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
authors.forename: Jun Hyuk
authors.initials: JH
authors.lastname: Hong
authors.forename: Geun Taek
authors.initials: GT
authors.lastname: Lee
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Seok Joo
authors.initials: SJ
authors.lastname: Kwon
authors.forename: Seok Hee
authors.initials: SH
authors.lastname: Park
authors.forename: Seong Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Isaac Yi
authors.initials: IY
authors.lastname: Kim
mesh_terms: D029404:Activin Receptors / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D055418:Bone Morphogenetic Protein 6 / Q000494:pharmacology / Q000502:physiology*; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000819:agonists / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D015398:Signal Transduction; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000819:agonists / Q000096:biosynthesis / Q000276:immunology
chemical_list: D055418:Bone Morphogenetic Protein 6; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D029404:Activin Receptors; D052006:Bone Morphogenetic Protein Receptors, Type II