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.
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.
Albert Einstein College of Medicine, Bronx, NY 10461.
J A
JA
Satriano
K
K
Hora
Z
Z
Shan
E R
ER
Stanley
T
T
Mori
D
D
Schlondorff
D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000096:biosynthesis* / Q000235:genetics; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism*; D007074:Immunoglobulin G / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D007074:Immunoglobulin G; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D005576:Colforsin; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D000242:Cyclic AMP