Nifedipine, a Calcium-channel Blocker, Inhibits Advanced Glycation End-product-induced Expression of Monocyte Chemoattractant Protein-1 in Human Cultured Mesangial Cells

Abstract

The interaction between advanced glycation end-products (AGEs) and their receptors mediates the progressive alteration in renal architecture and loss of renal function in diabetic nephropathy. This study investigated whether nifedipine, a widely used anti-hypertensive drug, suppresses expression of monocyte chemoattractant protein-1 (MCP-1), a chemokine that mediates the recruitment of monocytes to inflammatory sites, in AGE-exposed human cultured mesangial cells. Cells were treated with 100 μg/ml AGE-bovine serum albumin (BSA) or non-glycated BSA in the presence or absence of 1 μM nifedipine or 50 nM diphenylene iodonium, an inhibitor of reduced nicotinamide-adenine dinucleotide phosphate oxidase, for 4 or 24 h. Expression of MCP-1 mRNA was measured using a semi-quantitative reverse transcription-polymerase chain reaction; MCP-1 protein production was measured using an enzyme-linked immunosorbent assay. AGEs significantly increased both MCP-1 mRNA expression and protein production in mesangial cells; this increase was blocked by both nifedipine and diphenylene iodonium. These results suggest that nifedipine could play a protective role against early diabetic nephropathy by suppressing MCP-1 overexpression via blockade of AGE signalling in mesangial cells.