Objective: To investigate the influence of atorvastatin (ATOR) on the expression of monocyte chemoattractant protein-1 (MCP-1) induced by high concentration glucose in peritoneal mesothelial cells (PMCs) and the possible mechanism thereof.
Methods: Rt PMCs were isolated, cultured, passaged, and divided into 3 groups: (1) treated with glucose of the concentrations of 0.1, 1.5, 2.5, 4.25% respectively, (2) treated with 1.5% glucose for 0, 0.5, 1, 3, 12, 24, and 48 h respectively, (3) pretreated with ammonium pyrrolidinedithiocarbomate (PDTC) of the concentrations of 5, 10, 25, or 50 micromol/L for 2 h, and then treated with 1.5% glucose for 3 h; and (4) pretreated with ATOR of the concentrations of 0.1, 1, or 10 mmol/L for 24 h, and then treated with 1.5% glucose for 3 h. Western blotting was used to measure the expression of MCP-1, p65, and inhibitor of nuclear factor-kappaBalpha (IkappaBalpha). RT-PCR was used to measure the expression of MCP-1 mRNA.
Results: PMCs expressed MCP-1 in the normal condition. Glucose dose- and time-dependently reduced the protein expression of IkappaBalpha in the PMCs and increased the p65 expression in the nucleus, and accelerated the PMCs to express MCP-1 mRNA and protein (P < 0.05 and P < 0.01). PDTC dose-dependently inhibited the acceleration of expression of MCP-1 mRNA and protein in the PMCs induced by high concentration glucose (P < 0.05 or P < 0.01). ATOR dose-dependently increased the IkappaBalpha expression, decreased the p65 expression in nucleus, and decreased the expression of MCP-1 mRNA and protein (P < 0.05 or P < 0.01).
Conclusion: High concentration glucose induces PMCs to express MCP-1 in a time- and dose-dependent manner. Nuclear factor- kappaB (NF-kappaB) takes part in this regulation. ATOR inhibits PMCs to express MCP-1 through inhibiting NF-kappaB pathway.