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

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.