The high-mobility group box-1 (HMGB1), as a highly conserved ubiquitous DNA-binding protein, has been widely studied in various diseases, including inflammation and tumor; however, fewer studies were focused on the mechanisms controlling HMGB1 release compared with the function of HMGB1. Previous studies have proven that ANG II can act as a pro-inflammatory cytokine, both of HMGB1 and ANG II were significantly upregulated in autoimmune diseases; however, the exact role of ANG II in regulating HMGB1 release have not been shown. The present study was to define the effects of ANG II on macrophages and the possible mechanisms in controlling HMGB1 release. Our results showed that ANG II can induce M1 macrophage polarization through upregulated the expression of HMGB1 and caused acetylation of HMGB1 and release via its dissociation from SIRT1, which in a positive feedback upregulates ANG II. Subsequently, HMGB1 inhibitors can reduce the ANG II-elicited polarize of macrophage. Meanwhile, we show that JAK/STAT pathways play an essential role in ANG II-induced HMGB1 nuclear translocation, JAK/STAT specific inhibitors can inhibit ANG II-induced HMGB1 expression. Taken together, our results provide a novel evidence that HMGB1 play a critical role in ANG II mediated macrophage polarization, and we suggest that ANG II mediated HMGB1 release via dissociation from SIRT1, induce hyperacetylation of HMGB1, thus for subsequent release, suggesting that the angiotensin II receptor antagonist is a potential drug target for inhibiting HMGB1 release in inflammation diseases.
Keywords: Angiotensin II; HMGB1; SIRT1; hyperacetylation; macrophage reprogramming.
© 2018 International Federation for Cell Biology.