Nifedipine, a calcium-channel blocker, inhibits advanced glycation end-product-induced expression of monocyte chemoattractant protein-1 in human cultured mesangial cells.
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 microg/ml AGE-bovine serum albumin (BSA) or non-glycated BSA in the presence or absence of 1 microM 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.
Matsui
T
T
Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.
Yamagishi
S
S
Nakamura
K
K
Inoue
H
H
Takeuchi
M
M
D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects*; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D009543:Nifedipine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism
D002121:Calcium Channel Blockers; D018932:Chemokine CCL2; D017127:Glycation End Products, Advanced; D012333:RNA, Messenger; D009543:Nifedipine