Knockdown of TNF‑α alleviates acute lung injury in rats with intestinal ischemia and reperfusion injury by upregulating IL‑10 expression
| Autor: | Liu‑Lin Xiong, Shu‑Yuan Fan, Sheng‑Lan Wang, Piao Zhang, Xue‑Rong Zhang, Zhen Yang, Bing Yuan, Ting‑Hua Wang, Qiong Zhao, Zi‑Bing Zhang, Yun‑Hui Zhang |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine interleukin-10 Acute Lung Injury Lung injury Pharmacology Proinflammatory cytokine Rats Sprague-Dawley 03 medical and health sciences RNA interference 0302 clinical medicine medicine.artery Genetics medicine Animals Superior mesenteric artery Intestinal Mucosa RNA Small Interfering Lung Gene knockdown intestinal ischemia and reperfusion Oncogene Tumor Necrosis Factor-alpha business.industry Articles General Medicine respiratory system medicine.disease Rats Up-Regulation respiratory tract diseases Intestines RNAi Therapeutics 030104 developmental biology medicine.anatomical_structure Reperfusion Injury 030220 oncology & carcinogenesis Tumor necrosis factor alpha tumor necrosis factor-α business Reperfusion injury |
| Zdroj: | International Journal of Molecular Medicine |
| ISSN: | 1791-244X 1107-3756 |
| DOI: | 10.3892/ijmm.2018.3674 |
| Popis: | 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/R‑induced acute lung injury (ALI). Therefore, the present study aimed to investigate whether blocking tumor necrosis factor‑α (TNF‑α) expression could protect the lungs from injury following II/R, and to explore the possible underlying mechanism involving interleukin‑10 (IL‑10). 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 TNF‑α short hairpin (sh)RNA were injected into the right lung tissues, in order to induce TNF‑α knockdown. The severity of ALI was determined according to lung injury scores and lung edema (lung wet/dry weight ratio). The expression levels of TNF‑α were analyzed by quantitative polymerase chain reaction (qPCR), western blotting and immunofluorescence (IF) staining. IL‑10 expression, in response to TNF‑α 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 TNF‑α expression, in the lungs of II/R rats. Conversely, treatment with TNF‑α shRNA significantly alleviated the severity of ALI and upregulated the expression levels of IL‑10 in lung tissues. These findings suggested that TNF‑α RNA interference may exert a protective effect on II/R‑induced ALI via the upregulation of IL‑10. Therefore, TNF‑α knockdown may be considered a potential strategy for the prevention or treatment of ALI induced by II/R in future clinical trials. |
| Databáze: | OpenAIRE |
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