PRODUCTION AND CYTOKINE-MEDIATED REGULATION OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 BY HUMAN PROXIMAL TUBULAR EPITHELIAL-CELLS

Impairment of renal function in various types of glomerular disease is associated with tubulointerstitial changes. The mechanism of mononuclear cell infiltration in the interstitium is not fully understood. Recently, monocyte chemoattractant protein-1 (MCP-1) has been identified as a monocyte-specific chemotactic factor. We analyzed the presence of MCP-1 in renal biopsies from patients with various forms of glomerular disease and demonstrated that MCP-1 expression is increased in renal tubular epithelial cells during disease. Further analysis showed that various cell lines of human proximal tubular epithelial cells (PTEC) produce MCP-1 in culture under serum-free conditions and that the production is inhibited by cycloheximide. IL-1 alpha and TNF-alpha enhanced the production by each cell line in a dose- and time-dependent manner as measured by radioimmunoassay. Northern blot analysis demonstrated that IL-1 alpha and TNF-alpha markedly enhanced the expression of MCP-1 mRNA. Taken together these observations support the notion that MCP-1 is synthesized de novo by PTEC. MCP-1 produced by PTEC is found to be 13 kD by gel filtration chromatography. It is chemotactically active for monocytes. We conclude that in various types of glomerular disease, MCP-1 expression in tubular epithelial cells is associated with up-regulation of MCP-1 production by PTEC. These findings raise the possibility that macrophages may accumulate in renal interstitium as a consequence of MCP-1 production by PTEC.