IL-33 Enhances the Lipopolysaccharide-Induced Secretion of Inflammatory Cytokines and Ameliorates Lipopolysaccharide Desensitization in Macrophages

Abstract

Background: Lipopolysaccharide (LPS) desensitization, which is characterized by hyporesponsiveness and a form of immunosuppression, is important in the negative regulation of responses to LPS and inflammatory disease such as sepsis. However, effect of IL-33 in the desensitization to LPS remains unclear. Methods: We used RNA-sequencing technology to analyze changes in mRNA in bone-marrow-derived macrophages (BMDMs) stimulated with LPS. Changes in expression and secretion of inflammatory cytokines were detected by qPCR and ELISA, respectively. Mechanisms were further studied through p65 phosphorylation detection. Results: IL-33 expression was significantly increased in LPS-treated macrophages, indicating its involvement in LPS-induced inflammation. Exogenous IL-33 increased the inflammatory response and ameliorated LPS desensitization by increasing the secretion of proinflammatory cytokines. It also activated p65 phosphorylation in resistant cells. Conclusion: IL-33 can enhance the inflammatory response induced by LPS and ameliorate LPS desensitization possibly by activating the NF-κB pathway in mouse macrophages.