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.

Epithelial cells expressed IL-33 to promote degranulation of mast cells through inhibition on ST2/PI3K/mTOR-mediated autophagy in allergic rhinitis

“…[37]. In addition, IL-33, which was found to ameliorate experimental colitis in mice by inhibiting autophagy of macrophages [24], have a neuroprotective effect by inhibition on autophagy [22,23]. Similarly, our results also showed that IL-33/ST2 signaling pathway regulated the degranulation of mast cells through autophagy (Figures 2 and 5).…”

“…IL-33 is a recently discovered cytokine that is produced by specialized epithelial cells and plays important roles in the pathogenesis of various allergic diseases [19][20][21]. In addition, IL-33 is able to suppress autophagy and exerts neuroprotection functions [22,23] and ameliorates experimental colitis by promoting autophagy of macrophages [24]. It is, therefore, possible that epithelial cells regulate autophagy and degranulation of mast cells through IL-33, which could be a potential mechanism of the pathogenesis of AR.…”

Expression of IL-33 Receptor Is Significantly Up-Regulated in B Cells During Pregnancy and in the Acute Phase of Preterm Birth in Mice

“…Indeed, it has been shown that IL-33, thought to be ST2, induces B1 B cell activation, leading to a rapid proliferation and production of natural IgM (38). Besides inducing a Th2 immune response, the IL-33/ST2 axis has also been extensively demonstrated to participates in regulating immune homeostasis upon tissue injury (15,33,33,36,37,(63)(64)(65)(66)(67)(68)(69). In the context of pregnancy, Huang and co-authors have recently demonstrated that choriodecidual B1 B cells protect against inflammationinduced PTB by producing progesterone-induced blocking factor 1 (PIBF1) in response to the mucosal alarmin IL-33 (31).…”

Helicobacter pylori Induces IL-33 Production and Recruits ST-2 to Lipid Rafts to Exacerbate Inflammation

“…Statins promote autophagy fusion with lysosomes to reduce bacterial burdens in macrophages [26,50]. IL-33 treatment enhances autophagy in mice with experimental colitis [51]. Intranasal administration of IL-33 was shown to promote IL-13-dependent autophagy and that this axis regulated mucus secretion by airway epithelial cells [52].…”