Blocking CXCR1/2 contributes to amelioration of lipopolysaccharide‐induced sepsis by downregulating substance P

作者：Miaoshu Wang, Danfeng Zhong, Ping Dong, Yukang Song · 发表于：Journal of Cellular Biochemistry · 年份：2018 · DOI：10.1002/jcb.27507 · 被引用次数：11 · 研究领域：Immune Response and Inflammation、Sepsis Diagnosis and Treatment、Chemokine receptors and signaling

OBJECTIVES: C-X-C chemokine receptor types 1/2 (CXCR1/2) is known to be activated in liver damage in acute-on-chronic liver failure; however, the role in lipopolysaccharide (LPS)-induced sepsis is unknown. The current study was designed to determine whether or not CXCR1/2 blockade with reparixin ameliorates acute lung injury (ALI) by affecting neuropeptides in a LPS-induced sepsis mouse model. MATERIALS AND METHODS: Male C57BL/6 mice (10 to 14-week old) were divided into sham, LPS, sham-R, and LPS-R groups. Bronchoalveolar lavage fluid (BALF) was collected and evaluated. The lung histopathology was assessed by immunocytochemistry staining. Western blot analysis was used to measure myeloperoxidase, substance P (SP), and vasoactive intestinal peptide. RESULTS: LPS-induced animal models were ameliorated by cotreatment with a CXCR1/2 antagonist. Moreover, the protective effects of CXCR1/2 antagonists were attributed to the increased secretion of pro-opiomelanocortin and decreased the secretion of SP. Reparixin decreased the expression of necroptosis cell death markers induced by LPS. CONCLUSION: The results of this study indicate that blockade of CXCR1/2 may represent a promising therapeutic strategy for the treatment of sepsis-associated ALI through regulation of neuropeptides and necroptosis.