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Regulation of Monocyte Chemoattractant protein-1 and Macrophage Colony-Stimulating factor-1 by IFN-gamma, Tumor Necrosis Factor-Alpha, IgG Aggregates, and cAMP in Mouse Mesangial Cells

Regulation of Monocyte Chemoattractant protein-1 and Macrophage Colony-Stimulating factor-1 by IFN-gamma, Tumor Necrosis Factor-Alpha, IgG Aggregates, and cAMP in Mouse Mesangial Cells

J A Satriano, K Hora, Z Shan, E R Stanley, T Mori, D Schlondorff

J Immunol. 1993 Mar 1;150(5):1971-8.

PMID: 8382248

Abstract:

The interaction of mesangial cells and monocyte-macrophages plays an important role in renal glomerular immune injury. We have, therefore, examined the regulation of two monocyte-specific cytokines, i.e., macrophage CSF-1 and monocyte chemoattractant protein (MCP-1), the product of the mouse JE gene, in mouse mesangial cells. TNF-alpha, IFN-gamma, and aggregates of IgG increased the synthesis of CSF-1 (determined by RIA) and of MCP-1 (determined by biolabeling and immunoprecipitation). Stimulation of cAMP generation by forskolin or PGE2 decreased basal CSF-1 synthesis and attenuated the responses to TNF-alpha, IFN-gamma, and IgG. Forskolin and PGE2 also decreased biolabeled MCP-1 generation after stimulation with IFN-gamma, TNF-alpha, or IgG. By Northern blot analysis steady state levels of mRNA for CSF-1 and JE/MCP-1 were increased after incubation with IFN-gamma, TNF-alpha, or IgG, and these effects were attenuated by forskolin. By using nuclear run-on assays the decrease in CSF-1 and JE/MCP-1 mRNA levels induced by stimulation of cAMP generation with forskolin was attributed to decreased transcription of these genes. Thus, agents stimulating cAMP generation, including PGE2, counterbalance the generation of CSF-1 and JE/MCP-1 in response to IFN-gamma, TNF-alpha, and IgG complexes. The locally produced CSF-1 and MCP-1 may in turn influence the interaction between mesangial cells and monocyte-macrophages in glomerular injury.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413105	JE/MCP-1 (CCL2) from mouse			Price

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