The effect of green tea polyphenols on macrophage migration inhibitory factor-associated steroid resistance

Background Recently, evidence has been obtained to suggest that inflammation is provoked through upregulation of macrophage migration inhibitory factor (MIF) expression by steroids. However, little is known regarding the effect of steroids on MIF expression in human keratinocytes and the counter-effect of epigallocatechin-3-gallate (EGCG), a member of the class of green tea polyphenols. Objectives We determined whether or not steroids cause the upregulation of MIF in human keratinocytes, and if so, whether or not EGCG suppresses MIF upregulation in keratinocytes by steroids. We then assessed the effects of EGCG on MIF-induced Th-related chemokine and cytokine expression in keratinocytes. Methods HaCaT keratinocytes were first treated with dexamethasone in the presence or absence of EGCG in the culture medium. The keratinocytes were then treated with recombinant human (rh)-MIF in the presence or absence of EGCG in the culture medium. The expression of mRNA and protein in Th-related cytokines and chemokines, including MIF in the keratinocytes, was measured by real-time reverse transcription-polymerase chain reaction, Western blotting and enzyme-linked immunosorbent assay. Results Dexamethasone significantly enhanced MIF expression in human keratinocytes, and EGCG significantly downregulated the expression of dexamethasone induced MIF. EGCG also significantly downregulated rh-MIF-induced expression of Th-related cytokines and chemokines, such as interleukin (IL)-6, IL-18, transforming growth factor-beta, CCL17, CCL22 and CXCL10, in human keratinocytes. Conclusions These results demonstrated that EGCG may have a novel pharmacological effect to prevent steroid-induced tachyphylaxis and inflammation by suppressing the expression of MIF in human keratinocytes.