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Intestinal ischemia is a common clinical critical illness. Intestinal ischemia\u2010reperfusion (IIR) leads to acute lung injury (ALI), but the causative factors of ALI are unknown. The aim of this study was to reveal the causative factors and mechanisms of IIR\u2010induced lung injury. <jats:italic>Methods<\/jats:italic>. A mouse model of IIR was developed using C57BL\/6 mice, followed by detection of lung injury status and plasma levels of inflammatory factors in sham\u2010operated mice and model mice. Some model mice were treated with a tumor necrosis factor\u2010<jats:italic>\u03b1<\/jats:italic> (TNF\u2010<jats:italic>\u03b1<\/jats:italic>) inhibitor lenalidomide (10\u2009mg\/kg), followed by observation of lung injury status through hematoxylin and eosin staining and detection of neutrophil infiltration levels through naphthol esterase and Ly6G immunohistochemical staining. Additionally, peripheral blood polymorphonuclear neutrophils (PMNs) were cultured <jats:italic>in vitro<\/jats:italic> and then stimulated by TNF\u2010<jats:italic>\u03b1<\/jats:italic> to mimic <jats:italic>in vivo<\/jats:italic> inflammatory stimuli; this TNF\u2010<jats:italic>\u03b1<\/jats:italic> stimulation was also performed on PMNs after knockdown of FoxO3a or treatment with the c\u2010Jun N\u2010terminal kinase (JNK) inhibitor SP600125. PMN apoptosis after stimulation was detected using flow cytometry. Finally, the role of PMN apoptosis in IIR\u2010induced lung injury was evaluated <jats:italic>in vivo<\/jats:italic> by detecting the ALI status in the model mice administered with ABT\u2010199, a Bcl\u20102 inhibitor. <jats:italic>Results<\/jats:italic>. IIR led to pulmonary histopathological injury and increased lung water content, which were accompanied by increased plasma levels of inflammatory factors, with the TNF\u2010<jats:italic>\u03b1<\/jats:italic> plasma level showing the most pronounced increase. Inhibition of TNF\u2010<jats:italic>\u03b1<\/jats:italic> led to effective reduction of lung tissue injury, especially that of the damaging infiltration of PMNs in the lung. <jats:italic>In vitro<\/jats:italic> knockdown of FoxO3a or inhibition of JNK activity could inhibit TNF\u2010<jats:italic>\u03b1<\/jats:italic>\u2010induced PMN apoptosis. Further <jats:italic>in vivo<\/jats:italic> experiments revealed that ABT\u2010199 effectively alleviated lung injury and decreased inflammation levels by promoting PMN apoptosis during IIR\u2010induced lung injury. <jats:italic>Conclusion<\/jats:italic>. TNF\u2010<jats:italic>\u03b1<\/jats:italic> activates the JNK\/FoxO3a pathway to induce a delay in PMN apoptosis, which promotes IIR\u2010induced lung injury.<\/jats:p>","DOI":"10.1155\/2021\/8302831","type":"journal-article","created":{"date-parts":[[2021,12,30]],"date-time":"2021-12-30T02:35:14Z","timestamp":1640831714000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["TNF\u2010<i>\u03b1<\/i> Induces Neutrophil Apoptosis Delay and Promotes Intestinal Ischemia\u2010Reperfusion\u2010Induced Lung Injury through Activating JNK\/FoxO3a 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