Bone Morphogenetic Protein-7 Inhibits Constitutive and Interleukin-1β-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-β 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-1β-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-1β-induced monocyte chemotactic activity released from the mesangial cells. We examined the role of transcription factors NF-κB and AP-1 in BMP-7 inhibition of IL-1β-induced MCP-1 expression. IL-1β increased NF-κB and AP-1 activity and both transcription factors mediated IL-1β-induced MCP-1 expression in mesangial cells. BMP-7 inhibited IL-1β-induced AP-1 activity in a concentration-dependent manner. In contrast, IL-1β-induced NF-κB activity and IκBα degradation were not affected by BMP-7. Furthermore, IL-1β-induced phosphorylation of c-Jun N-terminal kinase was inhibited by BMP-7. These data suggest that BMP-7 inhibits constitutive and IL-1β-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.

A c-Jun NH2-Terminal Kinase Inhibitor SP600125 (Anthra[1,9-cd]pyrazole-6 (2H)-one) Blocks Activation of Pancreatic Stellate Cells

“…SP600125 here inhibited IL-1␤-or TNF-␣-induced MCP-1 expression, suggesting that JNK is required for optimal MCP-1 expression in PSCs. This is in agreement with the previous report showing that JNK was necessary for IL-1␤-induced MCP-1 expression in human mesangial cells (Lee et al, 2003). We have previously reported that ethanol and acetaldehyde at clinically relevant concentrations activated JNK, but they failed to induce MCP-1 expression in PSCs (Masamune et al, 2002b).…”

Involvement of Apoptosis Signal-Regulating Kinase-1 on Angiotensin II-Induced Monocyte Chemoattractant Protein-1 Expression

“…30 In the present study, DN-ASK and DN-p38MAPK inhibited the NF-B activities by angiotensin II and pyrrolidine dithiocarbamate inhibited MCP-1 mRNA expression by angiotensin II, thereby suggesting the important role of NF-B through ASK-1 and p38MAPK signaling on MCP-1 expression in cardiac fibroblasts. Although activation of JNK is reported to be important for MCP-1 gene expression in other type of cells, 31 angiotensin-II-induced JNK activation has no marked effects on MCP-1 expression in the present study. Because DN-p38MAPK inhibited and DN-JNK did not inhibit the activation of NF-B by angiotensin II in the present study, one of the reasons for different effects between JNK and p38MAPK on MCP-1 expression may be different NF-B activation in cardiac fibroblasts.…”

Analysis of spatial and temporal expression patterns of bone morphogenetic protein family members in the rat uterus over the estrous cycle

“…Thus, the increase in eosinophils at estrus does not appear to play a critical role in establishing uterine homeostasis. Nonetheless BMP-2 (Kim et al 1999, Willette et al 1999, BMP-4 (Cunningham et al 1992, Miyazaki et al 2003 and BMP-7 (Gould et al 2002, Lee et al 2003 have been linked to chemotaxis in a variety of cell types (including blood cells), leaving open the question of whether BMPs (in addition to IL-5 and eotaxin), might also play a role in eosinophil infiltration into the uterus. By in situ hybridization, we detected BMP-RIA and -RII in the myometrium.…”