title: Bone morphogenetic protein-7 inhibits constitutive and interleukin-1 beta-induced monocyte chemoattractant protein-1 expression in human mesangial cells: role for JNK/AP-1 pathway.
abstract: Bone morphogenetic protein-7 (BMP-7), which belongs to the TGF-beta superfamily, has been shown to reduce macrophage infiltration and tissue injury in animal models of inflammatory renal disease. To explore the mechanism involved in the anti-inflammatory effect, we investigated the effect of BMP-7 on monocyte chemoattractant protein-1 (MCP-1) expression in cultured human mesangial cells. BMP- 7 significantly inhibited constitutive and IL-1 beta-induced MCP-1 protein production and MCP-1 mRNA expression by mesangial cells in a time- and concentration-dependent manner. BMP-7 also inhibited IL-1 beta-induced monocyte chemotactic activity released from the mesangial cells. We examined the role of transcription factors NF-kappa B and AP-1 in BMP-7 inhibition of IL-1 beta-induced MCP-1 expression. IL-1 beta increased NF-kappa B and AP-1 activity and both transcription factors mediated IL-1 beta-induced MCP-1 expression in mesangial cells. BMP-7 inhibited IL-1 beta-induced AP-1 activity in a concentration-dependent manner. In contrast, IL-1 beta-induced NF-kappa B activity and I kappa B alpha degradation were not affected by BMP-7. Furthermore, IL-1 beta-induced phosphorylation of c-Jun N-terminal kinase was inhibited by BMP-7. These data suggest that BMP-7 inhibits constitutive and IL-1 beta-induced MCP-1 expression in human mesangial cells partly by inhibiting c-Jun N-terminal kinase activity and subsequent AP-1 activity, and provide new insight into the therapeutic potential of BMP-7 in the inflammatory renal diseases.
authors.affiliation: Renal Research Laboratory, Department of Internal Medicine, Medical College, Catholic University of Korea, Seoul, Korea.
authors.forename: Myung-Ja
authors.initials: MJ
authors.lastname: Lee
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Yang
authors.forename: Dong Chan
authors.initials: DC
authors.lastname: Jin
authors.forename: Yoon Sik
authors.initials: YS
authors.lastname: Chang
authors.forename: Byung Kee
authors.initials: BK
authors.lastname: Bang
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Kim
mesh_terms: D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology / Q000502:physiology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D016212:Transforming Growth Factor beta
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D016328:NF-kappa B; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; D016212:Transforming Growth Factor beta; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases