M2 macrophages have anti-inflammatory and wound healing activities and secrete anti-inflammatory cytokines. M2 macrophages are induced by Th2 cytokines such as IL-4 and IL-13. The development of therapeutics that can reduce inflammation through the induction of M2 macrophages is of considerable interest. Besides, cyclin-dependent kinase (CDK) 8 and its paralog, CDK19, are involved in regulation of gene transcription. CDK8/19 inhibition has been reported to promote regulatory T cells and thereby reduce inflammation. However, the influence of CDK8/19 inhibition on M2 macrophage polarization have not yet been investigated. We examine the role of BRD6989, a small-molecule CDK8/19 inhibitor, in induction of M2 macrophages.
RAW264.7 macrophages were pretreated with BRD6989, and then stimulated with IL-4. We analyzed the expression of CD206 and arginase-1 as markers of the M2 phenotype. BRD6989 enhanced the expression of IL-4-induced CD206 and arginase-1. Therefore, we suggested that BRD6989 enhances the effect of IL-4 on M2 macrophage polarity and we are currently investigating the mechanism in this regard.