Interleukin‑6 RNA knockdown ameliorates acute lung injury induced by intestinal ischemia reperfusion in rats by upregulating interleukin‑10 expression

Yuan,Bing; Xiong,Liu‑Lin; Wen,Mu‑Dong; Zhang,Piao; Ma,Hong‑Yu; Wang,Ting‑Hua; Zhang,Yun‑Hui

doi:10.3892/mmr.2017.6932

Interleukin‑6 RNA knockdown ameliorates acute lung injury induced by intestinal ischemia reperfusion in rats by upregulating interleukin‑10 expression

Authors:
- Bing Yuan
- Liu‑Lin Xiong
- Mu‑Dong Wen
- Piao Zhang
- Hong‑Yu Ma
- Ting‑Hua Wang
- Yun‑Hui Zhang
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Affiliations: Department of Respiration, First People's Hospital of Yunnan Province, Kunming, Yunnan 650000, P.R. China, Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan 650031, P.R. China
Published online on: July 6, 2017 https://doi.org/10.3892/mmr.2017.6932
Pages: 2529-2537
Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute lung injury (ALI) is a common complication following intestinal ischemia/reperfusion (II/R) injury and contributes to the associated high mortality rate. However, the underlying mechanism is poorly understood and treatments are limited. RNA interference (RNAi) has been demonstrated to provide a promising disease treatment strategy both in vitro and in vivo. Therefore, the present study aimed to test whether blocking the proinflammatory cytokine IL‑6 by RNAi may protect the lungs from remote organ injury following II/R, and to investigate the potential underlying mechanisms. A total of 176 adult healthy male Sprague‑Dawley rats were randomly divided into sham, II/R, negative‑control and IL‑6‑short hairpin (sh)RNA groups. The rats underwent II/R injury with occlusion of the superior mesenteric artery and coeliac artery to induce ischemia for 40 min, and were subsequently reperfused for 0‑48 h. The negative‑control group received a control lentiviral vector containing scrambled or non‑specific sequences, and the IL‑6‑shRNA groups were administered with a vector containing an IL‑6 shRNA sequence to affect RNAi‑mediated knockdown of IL‑6. ALI severity was determined by lung edema (lung wet/dry ratio) and histological analysis (lung injury scores). IL‑6 localization, and mRNA and protein expression levels, were detected by immunofluorescence, reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. IL‑10 expression induced by IL‑6 knockdown in lung tissues was additionally detected. IL‑6 RNAi was revealed to significantly reduce the expression of IL‑6, which was associated with upregulated IL‑10 expression in lung tissues. Consequently, the severities of ALI and edema induced by II/R were substantially improved. In conclusion, the present study demonstrated that IL‑6 RNAi may protect the lung from ALI induced by II/R, and that this protective role may be associated with upregulation of IL‑10. These findings may contribute to the development of an IL‑6‑RNAi‑based therapeutic strategy for the treatment of II/R‑induced ALI.

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