Heat shock transcription factor 2 reduces the secretion of IL-1β by inhibiting NLRP3 inflammasome activation in ulcerative colitis.

Abstract Ulcerative colitis (UC) is a chronic inflammatory disease with unknown aetiology. As a pro-inflammatory cytokine, interleukin-1β (IL-1β) plays a critical, damaging role in UC. Heat shock proteins (HSPs) are important anti-inflammatory factors that maintain intestinal epithelial cells (IECs) homeostasis. Heat shock transcription factor 2 (HSF2) is an important regulator of HSPs. In our previous research, we found that HSF2 is highly expressed in UC, is negatively related to colon inflammation of mice, and inhibits the expression of IL-1β, but the specific mechanism is still unclear. As a product of the NLRP3 inflammasome, the expression of IL-1β is closely related to NLRP3 inflammasome activation. Therefore, we hypothesised that HSF2 affects the secretion of IL-1β by regulating activation of the NLRP3 inflammasome. In this study, hsf-/- DSS model mice showed highest levels of expression of the NLRP3 inflammasome and the secretion of IL-1β. In Caco-2 cells, the levels of expression of the NLRP3 inflammasome and the secretion of IL-1β were inhibited by overexpression of HSF2, and inhibited HSF2 increased activation of the NLRP3 inflammasome and the secretion of IL-1β. These findings indicated that HSF2 might be an important target for inflammatory modulation in UC.