IL-10 mediates rosiglitazone-induced kidney protection in cisplatin nephrotoxicity.
Cisplatin, a major anti-neoplastic drug, is known to be nephrotoxic and inflammation-inducing. A peroxisome proliferator-activated receptor gamma agonist, regulating lipid metabolism, has known to have anti-inflammatory effect, but the protection mechanisms in various kidney injuries are not fully understood. The purpose of this study was to examine the reno-protective effect of rosiglitazone on cisplatin nephrotoxicity in mice focusing on inflammation and apoptosis. Male BALB/c mice were pretreated with rosiglitazone (10 mg/kg) or vehicle through daily intraperitoneal injection for 3 days and then were given a single injection of cisplatin (20 mg/kg). Cisplatin induced a significant rise in blood urea nitrogen and creatinine levels, and tubular cell damage with marked tissue inflammation. Tissue cytokines and chemokines measured by a cytometric bead array showed increased TNF-alpha, IL-6, MCP-1, and IFN-gamma levels, while IL-10, an anti-inflammatory cytokine, was significantly decreased by cisplatin treatment. However, rosiglitazone pretreatment substantially reversed the depressed IL-10 level with simultaneous suppression of proinflammatory cytokines and chemokines. This tissue cytokine and chemokine milieu was associated with marked attenuation of kidney injury elicited by cisplatin. These findings suggest that the rosiglitazone-mediated renoprotective effect in cisplatin nephrotoxicity of mice is partially mediated by upregulation of anti-inflammatory IL-10 production.
Kim
Myung-Gyu
MG
Division of Nephrology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea.
Yang
Ha Na
HN
Kim
Hye-Won
HW
Jo
Sang-Kyung
SK
Cho
Won Yong
WY
Kim
Hyoung-Kyu
HK
D058186:Acute Kidney Injury / Q000139:chemically induced*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D002945:Cisplatin / Q000633:toxicity*; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism* / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D047495:PPAR gamma / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
D018925:Chemokines; D016207:Cytokines; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D016753:Interleukin-10; D020169:Caspases; D002945:Cisplatin