1. These results support the hypothesis that CDK8/19 is involved in the regulation of arginase-1 expression and suggest that CDK8/19 regulates IL-4-dependent arginase-1 expression. Furthermore, the BRD6989-mediated increase in arginase-1 expression was also investigated in murine peritoneal macrophages. Peritoneal macrophages have been used as primary macrophages in several studies. The supporting results from the primary cells suggested that CDK8/19 inhibition induces arginase-1 expression in resident macrophages. Previous studies have confirmed that IL-4 acts on M2 polarization through the phosphorylation of;We found that IL-4 phosphorylates STAT6 in macrophages (Fig. 3)
2. prior studies have failed to identify major M1/M2 macrophage markers, such as CD86, CD206, iNOS, and arginase-1; therefore, the effect of CDK8/19 inhibition on M1/M2 macrophage polarization has remained unclear. The present study found that BRD6989 increases CD206 and arginase-1 expression in macrophages. Similarly, we observed that senexin A increased both arginase-1 (Supplementary Fig. 8) and CD206 expression (Supplementary Fig. 10) in macrophages. These results suggest that CDK8/19 inhibitors may induce M2 macrophages. In conclusion, our findings demonstrate that CDK8/19 inhibitors increase IL-4-induced arginase-1 expression through p38 MAPK activation in macrophages;However;Small-molecule CDK8/19 inhibitors