Effect of bone morphogenetic protein-6 on macrophages.
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.
Hong
Jun Hyuk
JH
Division of Urology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
Lee
Geun Taek
GT
Lee
Jae Ho
JH
Kwon
Seok Joo
SJ
Park
Seok Hee
SH
Kim
Seong Jin
SJ
Kim
Isaac Yi
IY
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
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