Intervention with cilostazol attenuates renal inflammation in streptozotocin-induced diabetic rats.
OBJECTIVE
An inflammatory reaction is commonly found in the pathogenesis of diabetic nephropathy (DN). Cilostazol, a type 3 phosphodiesterase (PDE) inhibitor, has been previously reported to be anti-inflammatory, independent of an anti-platelet property. In the present study, we evaluated the hypothesis that cilostazol has protective effects on diabetic nephropathy by modulating the inflammatory process.


METHODS
Cilostazol was administered (27 or 9 mg kg(-1)d(-1)) to streptozotocin (STZ)-induced diabetic rats for eight weeks. We studied the kidney expression of vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 by immunofluorescence, western blotting and real-time PCR. The renal monocyte chemoattractant protein (MCP)-1 and vascular endothelial growth factor (VEGF) levels were examined by ELISA. The nuclear factor (NF)-kappaB-DNA binding activity was assessed by electrophoresis mobility shift assay (EMSA).


RESULTS
Our results showed cilostazol inhibited diabetes-induced hypertrophy of the glomeruli and infiltration of inflammatory cells, as well as the increase in the VCAM-1 and ICAM-1 mRNA and protein expression, and MCP-1 and VEGF contents in the kidneys. Consistent with these findings, cilostazol attenuated the enhanced activation of NF-kappaB in diabetic rats.


CONCLUSIONS
These results demonstrate that the renoprotective effects of cilostazol may be mediated by its anti-inflammatory actions, including inhibition of NF-kappaB activation and the subsequent decrease in proinflammatory factors, such as VCAM-1, ICAM-1, MCP-1 and VEGF expression in kidneys of diabetic rats.
Wang
Furong
F
Shandong Provincial Hospital, Shandong University, Jinan, China.
Li
Mei
M
Cheng
Lin
L
Zhang
Tingguo
T
Hu
Jianting
J
Cao
Mingfeng
M
Zhao
Jiajun
J
Guo
Ruichen
R
Gao
Ling
L
Zhang
Xiumei
X
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018932:Chemokine CCL2 / Q000096:biosynthesis; D000077407:Cilostazol; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000096:biosynthesis; D009393:Nephritis / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016328:NF-kappa B; D013777:Tetrazoles; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D018799:Intercellular Adhesion Molecule-1; D013311:Streptozocin; D000077407:Cilostazol