CTRP6 suppresses neutrophil extracellular traps formation to ameliorate sepsis-induced lung injury through inactivation of ERK pathway

• Published in: Allergologia et immunopathologia Vol. 50; no. 6; pp. 53 - 59
• Main Authors: Li, Jing, Ruijing Xuan, Wu, Weidong, Yang Han, Jiani Guo, Meixia Yang
• Format: Journal Article
• Language: English
• Published: Murcia Codon Publications 01.01.2022
• Subjects: Adenoviruses; Antibodies; Bioinformatics; Cytokines; Edema; Epidemiology; Histology; Inflammation; Laboratory animals; Lavage; Lungs; Metabolism; Mortality; Neutrophils; Pathogens; Proteins; Sepsis; Tumor necrosis factor-TNF; United States > US; China; Germany
• ISSN: 0301-0546; 0301-0546; 1578-1267
• DOI: 10.15586/aei.v50i6.677

Background: Septic lung injury is associated with excessive neutrophil activation, while neu-trophil extracellular traps formation contributes to inflammatory lung injury in sepsis. C1q/ tumor necrosis factor–related protein-6 (CTRP6) is a paralog of adiponectin and exerts anti-inflammatory and antioxidant properties. The role of CTRP6 in sepsis-associated inflammatory lung injury was investigated in this study. Methods: Mice were injected with lipopolysaccharides (LPS) intraperitoneally to establish the mouse sepsis model. They were first tail-vein injected with adenovirus-mediated overexpression CTRP6 (Ad-CTRP6) and then subjected to the LPS injection. Pathological changes in lungs were detected by hematoxylin and eosin staining. Inflammation cytokine levels in bronchoalveolar lavage fluid were assessed by qRT-PCR and ELISA. Flow cytometry was used to detect the number of neutrophils in bronchoalveolar lavage fluid, and immunofluorescence was performed to assess neutrophil extracellular traps. Results: Lipopolysaccharides induced pulmonary congestion, interstitial edema, and alveolar wall thickening in the lungs, as well as upregulated lung histology score and wet/dry weight ratio. CTRP6 was reduced in lung tissues of septic mice. Injection with Ad-CTRP6 ameliorated extensive histopathological changes in LPS-induced mice and decreased lung histology score and wet/dry weight ratio. Overexpression of CTRP6 reduced the levels of TNF-α, IL-6, and IL-1β in septic mice. Injection with Ad-CTRP6 also decreased the number of neutrophils and down-regulated Cit-H3 and myeloperoxidase polymers in septic mice. Protein expression of p-ERK in septic mice was reduced by overexpression of CTRP6. Conclusion: CTRP6 attenuated septic lung injury, exerted anti-inflammatory effect, and sup-pressed neutrophil extracellular traps formation against sepsis through inactivation of extra-cellular signal-regulated kinase signaling.