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Licofelone Inhibits Interleukin‐18‐Induced Pro‐Inflammatory Cytokine Release and Cellular Proliferation in Human Mesangial Cells
Author(s) -
Wu YuanJun,
Xue Mei,
Chen Hui
Publication year - 2012
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2012.00882.x
Subject(s) - cytokine , mesangial cell , interleukin , monocyte , pharmacology , mapk/erk pathway , p38 mitogen activated protein kinases , chemistry , medicine , endocrinology , immunology , kinase , biology , biochemistry , kidney
Abstract Licofelone, a novel dual anti‐inflammatory drug that inhibits 5‐lipoxygenase (5‐ LOX ) and cyclooxygenase ( COX ), has recently been defined to have therapeutic effects in osteoarthritis. Both 5‐ LOX and COX play functional roles in the pathogenesis of glomerulonephritis in children as well. Interleukin‐18 is a pro‐inflammatory cytokine. It remains unclear whether licofelone can ameliorate inflammatory response of human mesangial cells ( HMC ) exposed to interleukin‐18. In this study, HMC were cultured and exposed to interleukin‐18 with or without pre‐treatment of licofelone. COX ‐2 and 5‐ LOX enzyme activities in mesangial cells were determined with chromometry or high‐performance liquid chromatography. Prostaglandin E 2, cysteinyl leukotriene, monocyte chemotactic protein‐1 and interferon‐γ concentrations in culture medium were measured using an enzyme‐linked immunosorbent assay. Western blotting was employed to detect phosphorylated mitogen‐activated protein kinases ERK 1/2, p38 and JNK 1/2 in HMC . It was found that licofelone attenuated interleukin‐18‐induced COX ‐2 enzyme activity in HMC and prostaglandin E 2 release in a dose‐dependent manner. Similarly, licofelone inhibited interleukin‐18‐induced 5‐ LOX enzyme activity and leukotriene release. Licofelone reduced interleukin‐18‐induced phosphorylation of p38 mitogen–activated protein kinase and suppressed monocyte chemotactic protein‐1 and interferon‐γ synthesis. Moreover, licofelone inhibited IL ‐18‐induced proliferation of mesangial cells. We conclude that licofelone inhibits interleukin‐18‐induced pro‐inflammatory cytokine release and cellular proliferation in HMC , which may represent a really interesting therapeutic approach for glomerulonephritis in children.