The role of TIPE2 in hemorrhagic shock-induced acute lung injury

Acute lung injury is the most severe complication of hemorrhagic shock and closely correlates with the mortality rate of hemorrhagic shock. TIPE2 is a critical regulator of inflammation and is implicated in the pathogenesis of various inflammatory diseases. However, its role in hemorrhagic shock-induced acute lung injury is unclear, and the underlying mechanisms remain to be elucidated. Therefore, the purpose of this study was to investigate the role of TIPE2 in hemorrhagic shock-induced acute lung injury and its underlying mechanisms.

C57BL/6J and TIPE2 knockout mice were used to establish hemorrhagic shock model, with a sham surgery as the control. The pulmonary ventilation function was evaluated using in-vivo testing system. Blood gas analysis was conducted to evaluate changes in blood oxygen level, reflecting the body's acid-base balance. Hematoxylin and eosin staining facilitated the observation of lesion progression in pulmonary tissue. The expression levels of TIPE2, myeloperoxidase, and citrullinated histone in lung tissues were determined by Western blotting, whereas the levels of tumor necrosis factor-α and IFN-γ in bronchoalveolar lavage fluid were quantified by enzyme-linked immunosorbent assay to evaluate the levels of key inflammatory mediators. VE-cadherin and E-cadherin expression in lung tissues were assessed by Western blotting to indicate changes of lung microvascular and alveolar permeability.

Following hemorrhagic shock, mice developed severe acute lung injury, characterized by impaired lung function, respiratory acidosis, structural damage, and pulmonary edema. This was accompanied by a heightened inflammatory response, evidenced by elevated neutrophil activity and pro-inflammatory cytokines, alongside impaired endothelial and epithelial barrier integrity. Notably, TIPE2 knockout conferred protection against hemorrhagic shock-induced lung injury in mice.

TIPE2 knockout attenuates hemorrhagic shock-induced acute lung injury through mechanisms involving downregulation of inflammatory-associated protein expression, suppression of proinflammatory cytokine release, and restoration of pulmonary barrier permeability.