Academic Journal
Inhibitors of IFN gene stimulators (STING) improve intestinal ischemia–reperfusion-induced acute lung injury by activating AMPK signaling
| العنوان: | Inhibitors of IFN gene stimulators (STING) improve intestinal ischemia–reperfusion-induced acute lung injury by activating AMPK signaling |
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| المؤلفون: | Mei Yang, Yu-Xia Ma, Ying Zhi, Hai-Bin Wang, Li Zhao, Peng-Sheng Wang, Jie-Ting Niu |
| المصدر: | European Journal of Medical Research, Vol 27, Iss 1, Pp 1-11 (2022) |
| بيانات النشر: | BMC, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Medicine |
| مصطلحات موضوعية: | Acute lung injury, Intestinal ischemia–reperfusion, STING, AMPK, Inflammation, Medicine |
| الوصف: | Abstract Background Acute lung injury (ALI) caused by intestinal ischemia–reperfusion is a life-threatening disease. Interferon gene stimulator (STING) is a cytoplasmic DNA sensor that participates in the initiation of the inflammatory response. This study aims to establish whether C-176 (STING inhibitor) improves ALI under intestinal ischemia–reperfusion conditions. Methods To induce ALI, 72 male C57BL/6 mice were subjected to intestinal ischemia for 60 min and reperfusion for 3 h. Through intraperitoneal injection, C-176, a selective STING inhibitor, was injected 30 min before surgical treatment; meanwhile, compound C, an antagonist of adenosine monophosphate-activated protein kinase (AMPK), was administered 30 min after surgery. Based on immunofluorescence and Western blot assays, post-ALI assessments included lung water content (TLW), bronchoalveolar lavage fluid (BALF) protein, H&E staining, Masson staining, pulmonary pyroptosis [Gasdermin-D (GSDMD), cleaved caspase-1], and apoptosis (TUNEL, cleaved caspase-3). Results C-176 administration significantly attenuated intestinal ischemia–reperfusion-mediated ALI; this effect was reflected by exacerbated TLW and BALF protein, aggravated lung injury score, elevated degree of pulmonary fibrosis, increased TUNEL- and GSDMD-positive cells, and upregulated phospho-AMPK, cleaved caspase-1, cleaved caspase-3 and IFNβ mRNA expression. Moreover, C-176 increased phospho-AMPK under ALI conditions. Nonetheless, compound C partially reversed these beneficial effects. Conclusion C-176, a selective STING inhibitor, improves intestinal ischemia–reperfusion-mediated ALI, and its underlying mechanism may be associated with AMPK signal activation. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2047-783X 09415742 |
| Relation: | https://doaj.org/toc/2047-783X |
| DOI: | 10.1186/s40001-022-00703-1 |
| URL الوصول: | https://doaj.org/article/e871bbf8ed064b4e86e09415742dc658 |
| رقم الانضمام: | edsdoj.871bbf8ed064b4e86e09415742dc658 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2047783X 09415742 |
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| DOI: | 10.1186/s40001-022-00703-1 |