Interleukin‐1α and tumour necrosis factor‐α modulate the production of monocyte chemoattractant protein‐1 by cultured human glomerular visceral epithelial cells

Abstract

Summary: Mediators released by glomerular macrophages may stimulate glomerular visceral epithelial cells (GVEC) to produce cytokines, growth factors or extracellular matrix components. This study describes that human GVEC produce monocyte chemoattractant protein‐1 (MCP‐1), a monocyte‐specific chemotactic factor, and the effects of interleukin‐lα (IL‐1α) and tumour necrosis factor‐α (TNF‐a) on the production of MCP‐1 by GVEC.We observed that the intensity of MCP‐1 staining in GVEC is stronger in membranous nephropathy and glomerulosclerosis than in normal kidneys. Various cell lines of GVEC produced significant amounts of MCP‐1, as assessed by inhibition radio‐immunoassay. the presence of IL‐1α and TNF‐α during culture of GVEC enhanced the production of MCP‐1 in a dose‐ and time‐dependent manner. Glomerular visceral epithelial cells in culture express mRNA for MCP‐1 and the expression is upregulated 2.0‐ and 1.4‐fold in the presence of optimal concentration of IL‐1α and TNF‐α, respectively. De novo synthesis of MCP‐1 is supported by the observation that MCP‐1 production is fully inhibited by cydoheximide. Monocyte chemoattractant protein‐1 isolated from GVEC supernatants exhibits a molecular size of 12 and 10 kDa as determined by gel filtration chromatography. Both sizes of MCP‐1 is chemotactically active for monocytes.This study shows increased MCP‐1 production by cultured human GVEC after stimulation with the inflammatory cytokines IL‐1α and TNF‐α. the expression of MCP‐1 in GVEC was found to be upregulated in membranous nephropathy and glomerulosclerosis. These findings suggest that MCP‐1 may be involved in glomerular injury in these diseases. the possible role of MCP‐1 in the pathogenesis of human glomerulonephritis is discussed.