title: Bone morphogenetic protein 6-induced interleukin-1β expression in macrophages requires PU.1/Smad1 interaction.
abstract: Interleukin 1β (IL-1β) is a pro-inflammatory cytokine secreted by activated macrophages and monocytes. Previously, we have reported that bone morphogenetic protein-6 (BMP-6) induces inducible nitric oxide synthase (iNOS) expression via IL-1β in macrophages. In the present study, we demonstrate that BMP-6 increases IL-1β expression in macrophages via the receptors ALK3 and BMPRII as well as the downstream signaling protein Smad1. Surprisingly though, inhibition of the ERK and JNK non-Smad pathways also completely blocked the induction of IL-1β by BMP-6 in macrophages. Further analysis revealed that a physical interaction between the transcription factor PU.1 and Smad 1 is necessary for the upregulation of IL-1β expression by BMP-6 in macrophages. Taken together, these results demonstrate that BMP-6-induced IL-1β expression in macrophages is mediated via a cross-talk between the Smad and the non-Smad pathways through Smad1 and PU.1.
authors.affiliation: Section of Urologic Oncology and the Dean and Betty Gallo Prostate Cancer Center, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, 195 Little Albany Street #4560, New Brunswick, NJ 08903, United States.
authors.forename: Geun Taek
authors.initials: GT
authors.lastname: Lee
authors.forename: Yeon Suk
authors.initials: YS
authors.lastname: Jung
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.forename: Isaac Yi
authors.initials: IY
authors.lastname: Kim
mesh_terms: D000818:Animals; D055418:Bone Morphogenetic Protein 6 / Q000378:metabolism*; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000378:metabolism; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000378:metabolism; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005455:Fluorescent Antibody Technique; D015151:Immunoblotting; D047468:Immunoprecipitation; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051898:Smad1 Protein / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D055418:Bone Morphogenetic Protein 6; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II; D048049:Extracellular Signal-Regulated MAP Kinases; D053583:Interleukin-1beta; D048031:JNK Mitogen-Activated Protein Kinases; D052247:Nitric Oxide Synthase Type II; D011518:Proto-Oncogene Proteins; D051898:Smad1 Protein; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C498212:Bmpr1a protein, mouse; C498219:Bmpr2 protein, mouse