High mobility group box-1 protein (HMGB-1) is one of the most important DAMPs and has been previously shown to promote the formation of the NOD-like receptor with pyrin domain containing-3 (NLRP3) inflammasome in microglia. Interleukin 4 (1L4) is a Th2-derived cytokine that plays a significant role in the function of various immune cells. However, the underlying molecular mechanism by which 1L4 signaling antagonizes NLRP3 inflammasome is poorly characterized. In particular, whether IL4 could modulate NLRP3 inflammasome in astrocytes remains unknown. In the present study, we elucidated this phenomenon and the mechanism by which 1L4 inhibits HMGB1-mediated NLRP3 inflammasome formation in astrocytes. For this purpose, we cultured and extracted primary astrocytes, setup different concentrations of HMGB1, and used immunofluorescence and western blotting to detect NLRP3 inflammasome formation, including NLRP3, ASC and caspase-1, and signaling changes in the nuclear factor KB (NF-kappa B). Meanwhile, BAY 11-7082 and IL4 were added with HMGB1 to observe the NLRP3 inflammasome and changes in NF-kappa B expression. Our data showed that HMGB1 could effectively promote NLRP3 inflammasome formation by activating NF-kappa B in astrocytes. This effect can be inhibited by BAY 11-7082, a NF-kappa B inhibitor. Meanwhile, IL4 could activate PPAR gamma via the STAT6 singling pathway and inhibit NF-kappa B activation, significantly decreasing formation of the NLRP3 inflammasome complex. Our study demonstrated that the NLRP3 inflammasome complex is also expressed in astrocytes, and IL4 could inhibit HMGB1-mediated NLRP3 inflammasome formation, through negative regulation of NF-kappa B activity and promotion of PPAR gamma activation. (C) 2018 Published by Elsevier Inc.