Effect of high glucose concentration on the synthesis of monocyte chemoattractant protein-1 in human peritoneal mesothelial cells: Involvement of protein kinase C

Human peritoneal mesothelial cells (HMC) contribute to the activation and c ontrol of inflammatory processes in the peritoneum by their potential to pr oduce various inflammatory mediators. The present study was designed to ass ess the effect of glucose, the osmotic active compound in most commercially available peritoneal dialysis fluids, on the synthesis of the C-C chemokin e monocyte chemoattractant protein-1 (MCP-1) in cultured HMC. The MCP-1 con centration in the cell supernatants was determined by enzyme-linked immunos orbent assay and the MCP-1 mRNA expression was examined using Northern blot analysis. Incubation of HMC with glucose (30-120 mM) resulted in a time- a nd concentration-dependent increase in MCP-1 protein secretion and mRNA exp ression. After 24 h the MCP-1 synthesis was increased from 2.8 +/- 0.46 to 4.2 +/- 0.32 ng/10(5) cells (n = 5, p < 0.05) in HMC treated with 60 mM glu cose. In contrast, osmotic control media containing either the metabolicall y inert monosaccharide mannitol or NaCl did not influence MCP-1 production. The stimulating effect of high glucose on MCP-1 expression in HMC was mimi cked by activation of protein kinase C (PKC) with the phorbol ester PMA (20 nM). Coincubation of the cells with glucose and the specific PKC inhibitor Ro 31-8220 completely blunted glucose-mediated MCP-1 expression. In summar y, our results indicate that glucose induces MCP-1 synthesis by a PKC-depen dent pathway. Since osmotic control media did not increase MCP-1 release, i t is suggested that the effect of glucose is mainly related to metabolism a nd not to hyperosmolarity. These data may in part explain elevated steady-s tate levels of MCP-1 found in the dialysis effluent of continuous ambulator y peritoneal dialysis patients. Copyright <(c)> 2001 S. Karger AG. Basel.