Inhibition of zymosan-induced cytokine and chemokine expression in human corneal fibroblasts by triptolide  

作　　者：Yang Liu Jing Li Ye Liu Ping Wang Hui Jia 

机构地区：[1]Department of Ophthalmology, First Hospital of Jilin University [2]Department of Pathology, First Hospital of Jilin University [3]Department of Otolaryngology-Head and Neck Surgery,First Hospital of Jilin University

出　　处：《International Journal of Ophthalmology(English edition)》2016年第1期9-14,共6页国际眼科杂志（英文版）

基　　金：Supported by the National Natural Science Foundation of China(No.81100635);the Norman Bethune Program of Jilin University(No.2012213)

摘　　要：AIM：To investigate the effects of triptolide on proinflammatory cytokine and chemokine expression induced by the fungal component zymosan in cultured human corneal fibroblasts（HCFs）.·METHODS：HCFs were cultured in the absence or presence of zymosan or triptolide.The release of interleukin（IL）-6,IL-8,and monocyte chemoattractant protein-1（MCP-1）into culture supernatants was measured with enzyme-linked immunosorbent assays.The cellular abundance of the m RNAs for these proteins was determined by reverse transcription and real-time polymerase chain reaction analysis.The phosphorylation of mitogen-activated protein kinases（MAPKs）and the endogenous nuclear factor-κB（NF-κB）inhibitor IκB-αwas examined by immunoblot analysis.The release of lactate dehydrogenase（LDH）activity from HCFs was measured with a colorimetric assay.·R ESULTS：Triptolide inhibited the zymosan-induced release of IL-6,IL-8,and MCP-1 from HCFs in a concentration-and time-dependent manner.It also inhibited the zymosan-induced up-regulation of IL-6,IL-8,and MCP-1 m RNA abundance in these cells.Furthermore,triptolide attenuated zymosan-induced phosphorylation of the MAPKs extracellular signalregulated kinase（ERK）,c-Jun NH2-terminal kinase（JNK）,and p38 as well as the phosphorylation and degradation of IκB-α.Triptolide did not exhibit cytotoxicity for HCFs.·C ONCLUSION：Triptolide inhibited proinflammatory cytokine and chemokine production by HCFs exposed tozymosan,with this action likely being mediated by suppression of MAPK and NF-κB signaling pathways.This compound might thus be expected to limit the infiltration of inflammatory cells into the cornea associated with fungal infection.AIM：To investigate the effects of triptolide on proinflammatory cytokine and chemokine expression induced by the fungal component zymosan in cultured human corneal fibroblasts（HCFs）.·METHODS：HCFs were cultured in the absence or presence of zymosan or triptolide.The release of interleukin（IL）-6,IL-8,and monocyte chemoattractant protein-1（MCP-1）into culture supernatants was measured with enzyme-linked immunosorbent assays.The cellular abundance of the m RNAs for these proteins was determined by reverse transcription and real-time polymerase chain reaction analysis.The phosphorylation of mitogen-activated protein kinases（MAPKs）and the endogenous nuclear factor-κB（NF-κB）inhibitor IκB-αwas examined by immunoblot analysis.The release of lactate dehydrogenase（LDH）activity from HCFs was measured with a colorimetric assay.·R ESULTS：Triptolide inhibited the zymosan-induced release of IL-6,IL-8,and MCP-1 from HCFs in a concentration-and time-dependent manner.It also inhibited the zymosan-induced up-regulation of IL-6,IL-8,and MCP-1 m RNA abundance in these cells.Furthermore,triptolide attenuated zymosan-induced phosphorylation of the MAPKs extracellular signalregulated kinase（ERK）,c-Jun NH2-terminal kinase（JNK）,and p38 as well as the phosphorylation and degradation of IκB-α.Triptolide did not exhibit cytotoxicity for HCFs.·C ONCLUSION：Triptolide inhibited proinflammatory cytokine and chemokine production by HCFs exposed tozymosan,with this action likely being mediated by suppression of MAPK and NF-κB signaling pathways.This compound might thus be expected to limit the infiltration of inflammatory cells into the cornea associated with fungal infection.

关 键 词：fungal keratitis ZYMOSAN TRIPTOLIDE INFLAMMATION comeal fibroblast 

分 类 号：R772.2[医药卫生—眼科]