Regulation of monocyte chemoattractant protein-1 and macrophage colony- stimulating factor-1 by IFN-γ, tumor necrosis factor-α, IgG aggregates, and cAMP in mouse mesangial cells

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

Research output: Contribution to journalArticle

146 Scopus citations

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-α, IFN-γ, 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-α, IFN-γ, and IgG. Forskolin and PGE2 also decreased biolabeled MCP-1 generation after stimulation with IFN-γ, TNF-α, or IgG. By Northern blot analysis steady state levels of mRNA for CSF-1 and JE/MCP-1 were increased after incubation with IFN-γ, TNF-α, 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-γ, TNF-α, 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.

Original languageEnglish (US)
Pages (from-to)1971-1978
Number of pages8
JournalJournal of Immunology
Volume150
Issue number5
StatePublished - Jan 1 1993

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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