Open Access

Knockdown of TNF‑α alleviates acute lung injury in rats with intestinal ischemia and reperfusion injury by upregulating IL‑10 expression

  • Authors:
    • Zhen Yang
    • Xue‑Rong Zhang
    • Qiong Zhao
    • Sheng‑Lan Wang
    • Liu‑Lin Xiong
    • Piao Zhang
    • Bing Yuan
    • Zi‑Bing Zhang
    • Shu‑Yuan Fan
    • Ting‑Hua Wang
    • Yun‑Hui Zhang
  • View Affiliations

  • Published online on: May 14, 2018     https://doi.org/10.3892/ijmm.2018.3674
  • Pages: 926-934
  • Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.
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August-2018
Volume 42 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Yang Z, Zhang XR, Zhao Q, Wang SL, Xiong LL, Zhang P, Yuan B, Zhang ZB, Fan SY, Wang TH, Wang TH, et al: Knockdown of TNF‑α alleviates acute lung injury in rats with intestinal ischemia and reperfusion injury by upregulating IL‑10 expression. Int J Mol Med 42: 926-934, 2018
APA
Yang, Z., Zhang, X., Zhao, Q., Wang, S., Xiong, L., Zhang, P. ... Zhang, Y. (2018). Knockdown of TNF‑α alleviates acute lung injury in rats with intestinal ischemia and reperfusion injury by upregulating IL‑10 expression. International Journal of Molecular Medicine, 42, 926-934. https://doi.org/10.3892/ijmm.2018.3674
MLA
Yang, Z., Zhang, X., Zhao, Q., Wang, S., Xiong, L., Zhang, P., Yuan, B., Zhang, Z., Fan, S., Wang, T., Zhang, Y."Knockdown of TNF‑α alleviates acute lung injury in rats with intestinal ischemia and reperfusion injury by upregulating IL‑10 expression". International Journal of Molecular Medicine 42.2 (2018): 926-934.
Chicago
Yang, Z., Zhang, X., Zhao, Q., Wang, S., Xiong, L., Zhang, P., Yuan, B., Zhang, Z., Fan, S., Wang, T., Zhang, Y."Knockdown of TNF‑α alleviates acute lung injury in rats with intestinal ischemia and reperfusion injury by upregulating IL‑10 expression". International Journal of Molecular Medicine 42, no. 2 (2018): 926-934. https://doi.org/10.3892/ijmm.2018.3674