IL-37 Gene Modification Enhances the Protective Effects of Mesenchymal Stromal Cells on Intestinal Ischemia Reperfusion Injury

• DOI: 10.21203/rs.2.23662/v1
• Publication Date: 2020-02-17T15:45:32Z
• Authors: Dejun Kong; Yonghao Hu; Xiang Li; Dingding Yu; Hongyue Li; Yiming Zhao; Yafei Qin; Wang Jin; Baoren Zhang; Bo Wang; Hongda Wang; Guangming Li; Hao Wang
• Keywords: Proinflammatory cytokine

Abstract Background : Ischemia reperfusion injury (IRI) is the major cause of intestinal damage in clinic. Although either mesenchymal stromal cells (MSCs) or interleukin 37 (IL-37) showed some beneficial roles to ameliorate IRI, their effects are limited. In this study, protective IL-37 gene-modified MSCs (IL-37-MSCs) for better prevention IRI investigated. Methods Intestinal model was established by occluding superior mesenteric artery 30min and then reperfusing 72 hours rats. Forty adult male SD rats were randomly divided into sham control, IL-37-MSC-treated, MSC-treated, recombinant (rIL-37)-treated untreated groups. assessed H&E staining. The levels gut barrier function factors (diamine oxidase D-Lactate) inflammation reactivity cytokine IL-1β assayed ELISA. expressions tissue damage-related NLRP3 inflammasome relative proteins including clevead caspase-1, IL-18 detected western blot. As downstream IL-18, mRNA proinflammatory mediators IL-6 TNF-α determined qPCR. Data analyzed one-way analysis variance among Results IL-37-MSCs able migrate damaged significantly inhibit IRI. compared with rIL-37 monotherapy group, IL-37-MSC treatment not only improved but also decreased local systemic level addition, (cleaved 4 IL-18) treated IL-37-MSCs. Furthermore, related markedly following treatment. Conclusion results suggest that gene modification enhance against NLRP3-related signaling pathways could be associated mediated protection.