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.
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 sepsismouse 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.
Authors: Stefan Bernhard; Stefan Hug; Alexander Elias Paul Stratmann; Maike Erber; Laura Vidoni; Christiane Leonie Knapp; Bertram Dietrich Thomaß; Michael Fauler; Bo Nilsson; Kristina Nilsson Ekdahl; Karl Föhr; Christian Karl Braun; Lisa Wohlgemuth; Markus Huber-Lang; David Alexander Christian Messerer Journal: J Innate Immun Date: 2021-04-15 Impact factor: 7.349