Slit2-Robo4 Signal Pathway and Tight Junction in Intestine Mediate LPS-Induced Inflammation in Mice

Abstract

Abstract Sepsis is one of the most common clinical diseases, which is characterized by a serious and uncontrollable inflammatory response. LPS-induced inflammation is a critical pathological event in sepsis, but the underlying mechanism has not yet been fully elucidated up to now. Here we reported that C57BL/6J mice injected with LPS (5 mg/kg, i.p.) for twenty-four hours could exhibit severe inflammatory reaction including an increased IL-1β, IL-18 in serum and activation of NLRP3 inflammasome in intestine. The injection of VX765 (10 mg/kg, i.p.), an inhibitor of NLRP3 inflammasome, could reverse these effects induced by LPS. The further experiment results of western blot and immunohistochemistry showed that Slit2 and Robo4 were significant decreased in intestine of LPS group, while the expression of VEGF was significant increased. Meanwhile, the protein level of tight junction protein ZO-1, occludin, and claudin-5 were significantly lower than in control group, which could also be reversed by VX765 injection. These results indicated that the increased level of IL-1β and IL-18 in serum induced by LPS is related to the increased intestinal permeability and activation of NLRP3 inflammasome. Altogether, our findings revealed that Slit2-Robo4 signaling pathway and tight junction in intestine may be involved in LPS-induced inflammation in mice, which may account for the molecular mechanism of sepsis.