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Knockdown of TNFα alleviates acute lung injury in rats with intestinal ischemia and reperfusion injury by upregulating IL10 expression

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Intestinal ischemia and reperfusion (II/R) injury often triggers severe injury in remote organs, with the lungs being considered the main target. Excessive elevation of proinflammatory cytokines is a major contributor in the occurrence and development of II/Rinduced acute lung injury (ALI). Therefore, the present study aimed to investigate whether blocking tumor necrosis factorα (TNFα) expression could protect the lungs from injury following II/R, and to explore the possible underlying mechanism involving interleukin10 (IL10). Briefly, II/R was induced in rats by 40 min occlusion of the superior mesenteric artery and celiac artery, followed by 8, 16 or 24 h of reperfusion. Subsequently, lentiviral vectors containing TNFα short hairpin (sh)RNA were injected into the right lung tissues, in order to induce TNFα knockdown. The severity of ALI was determined according to lung injury scores and lung edema (lung wet/dry weight ratio). The expression levels of TNFα were analyzed by quantitative polymerase chain reaction (qPCR), western blotting and immunofluorescence (IF) staining. IL10 expression, in response to TNFα knockdown, was detected in lung tissues by qPCR and IF. The results detected marked inflammatory responses, and increased levels of lung wet/dry weight ratio and TNFα expression, in the lungs of II/R rats. Conversely, treatment with TNFα shRNA significantly alleviated the severity of ALI and upregulated the expression levels of IL10 in lung tissues. These findings suggested that TNFα RNA interference may exert a protective effect on II/Rinduced ALI via the upregulation of IL10. Therefore, TNFα knockdown may be considered a potential strategy for the prevention or treatment of ALI induced by II/R in future clinical trials.
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Document Type: Research Article

Affiliations: 1: Department of Respiration, First People's Hospital of Yunnan Province, Kunming, Yunnan 650032, P.R. China 2: Department of Anesthesiology, Sun YatSen Memorial Hospital, Sun YatSen University, Guangzhou, Guangdong 510120, P.R. China 3: Department of Anesthesiology and Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China 4: Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan 650500, P.R. China

Publication date: January 1, 2018

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  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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