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Inhibitory Effect of Triptolide on Chemokine Expression Induced by Proinflammatory Cytokines in Human Corneal Fibroblasts

¹From the Departments of Biomolecular Recognition and Ophthalmology and ³Ocular Pathophysiology, Yamaguchi University School of Medicine, Ube City, Japan; and the ²Department of Ophthalmology, Jilin University School of Medicine, Changchun, China.

PURPOSE. Synthesis of various chemokines, including interleukin (IL)-8 and monocyte chemotactic protein (MCP)-1, as well as the surface expression of intercellular adhesion molecule (ICAM)-1 in corneal fibroblasts contribute to corneal inflammation. The effects of triptolide, the major constituent of extracts of the herb Tripterygium wilfordii hook f, on the expression of these proteins in human corneal fibroblasts were examined in comparison with those of dexamethasone.

METHODS. The release of IL-8 and MCP-1 from and the surface expression of ICAM-1 on cultured corneal fibroblasts were measured with enzyme-linked immunosorbent assays. The cellular abundance of the mRNAs for these proteins was determined by reverse transcription and real-time polymerase chain reaction analysis. The activities of the transcription factors NF-B and AP-1 were assessed by cell transfection with secretory alkaline phosphatase reporter genes.

RESULTS. Both triptolide and dexamethasone inhibited in a dose-dependent manner the expression of IL-8 and MCP-1 in corneal fibroblasts induced by the proinflammatory cytokines IL-1ß or tumor necrosis factor (TNF)-. These inhibitory effects were apparent at both the mRNA and protein levels. Both compounds also had a lesser inhibitory effect on cytokine-induced ICAM-1 expression. The activation of NF-B by IL-1ß was markedly inhibited by both triptolide and dexamethasone, whereas the activity of AP-1 was not affected by either agent.

CONCLUSIONS. Like dexamethasone, triptolide inhibited IL-8 and MCP-1 expression in cultured human corneal fibroblasts exposed to proinflammatory cytokines, an action most likely mediated by inhibition of NF-B activation. Similar effects of triptolide in vivo may be expected to limit the infiltration of neutrophils and monocytes into the cornea.

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