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

• Published in: The Journal of immunology (1950) 2003-03, Vol.170 (5), p.2557-2563
• Main Authors: Lee, Myung-Ja, Yang, Chul Woo, Jin, Dong Chan, Chang, Yoon Sik, Bang, Byung Kee, Kim, Yong-Soo
• Format: Article
• Language: English
• Subjects: Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins - pharmacology; Bone Morphogenetic Proteins - physiology; Cells, Cultured; Chemokine CCL2 - antagonists & inhibitors; Chemokine CCL2 - biosynthesis; Chemokine CCL2 - metabolism; Chemokine CCL2 - physiology; Enzyme Inhibitors - pharmacology; Glomerular Mesangium - cytology; Glomerular Mesangium - enzymology; Glomerular Mesangium - immunology; Glomerular Mesangium - metabolism; Humans; Interleukin-1 - antagonists & inhibitors; Interleukin-1 - pharmacology; JNK Mitogen-Activated Protein Kinases; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; Mitogen-Activated Protein Kinases - physiology; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; Phosphorylation; Protein Synthesis Inhibitors - pharmacology; Recombinant Proteins - pharmacology; RNA, Messenger - antagonists & inhibitors; RNA, Messenger - biosynthesis; Signal Transduction - immunology; Transcription Factor AP-1 - antagonists & inhibitors; Transcription Factor AP-1 - metabolism; Transcription Factor AP-1 - physiology; Transforming Growth Factor beta
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.170.5.2557

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.