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.·RESULTS: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.·CONCLUSION: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 (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 (IκB-αwas examined by immunoblot analysis. The release of lactate dehydrogenase (LDH) activity from HCFs was measured with a colorimetric assay. · RESULTS: 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-ind uced up-regulation of IL-6, IL-8, and MCP-1 m RNA abundance in these cells. Frtherrtherm, 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. · CONCLUSION: 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 may thus be expected to limit the infiltration of inflammatory cells into the cornea associated with fungal infection.