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

• Jing Li ^[2] ; Ruijing Xuan ^[1] ; Weidong Wu ^[2] ; Yang Han ^[2] ; Jiani Guo ^[2] ; Meixia Yang ^[2]
  1. [1] Shanxi Medical University

     Shanxi Medical University

     China

     
  2. [2] Department of Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China
• Localización: Allergologia et immunopathologia: International journal for clinical and investigate allergology and clinical immunology, ISSN-e 1578-1267, ISSN 0301-0546, Vol. 50, Nº. 6, 2022, págs. 53-59
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • Background: Septic lung injury is associated with excessive neutrophil activation, while neutrophil 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 downregulated 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 suppressed neutrophil extracellular traps formation against sepsis through inactivation of extracellular signal-regulated kinase signaling.