IL-33 ameliorates experimental colitis involving regulation of autophagy of macrophages in mice

Abstract

BackgroundPreviously, we have demonstrated that IL-33 administration protecting TNBS-induced experimental colitis is associated with facilitation of Th2/Tregs responses in mice. However, whether IL-33 regulates autophagy to ameliorate experimental colitis is unclear.ResultsIL-33 administration (2 μg/day, intraperitoneal injection), while facilitating Th2/Tregs responses, also enhances the autophagy in mice with TNBS-induced colitis as well as macrophages. In the meantime, we observed that inhibition of the autophagy with 3-methyladenine (3-MA) (24 mg/kg, intraperitoneal injection) in mice exacerbates TNBS-induced experimental colitis. On the contrary, administration of rapamycin (2 mg/kg,intragastric administration), an autophagy-enhancer, alleviates the colitis in mice. In vivo, Immunofluorescence analysis revealed that TNBS combined with IL-33 enhanced the autophagy of macrophages in the inflammatory gut tissue. In vitro, treatment with IL-33 promoted the autophagy of macrophages generated from bone marrow cells in dose-dependant manner. Furthermore, the effect of autophagy-enhancement by IL-33 is TLR4 signaling pathway dependant. Our notion was further confirmed by IL-33-deficient bone marrow-derived macrophages cells.ConclusionsIL-33 regulates the autophagy is a new immunoregulatory property on TNBS-induced experimental colitis in mice.