2. Academic Validation
  3. Necroptosis signaling and NLRP3 inflammasome cross-talking in epithelium facilitate Pseudomonas aeruginosa mediated lung injury

Necroptosis signaling and NLRP3 inflammasome cross-talking in epithelium facilitate Pseudomonas aeruginosa mediated lung injury

  • Biochim Biophys Acta Mol Basis Dis. 2022 Dec 2;166613. doi: 10.1016/j.bbadis.2022.166613.
Haoyang Li 1,  Jieying Guan 1,  Jiaqian Chen 1,  Weimin Sun 1,  Honglv Chen 1,  Yuhuan Wen 1,  Qile Chen 1,  Shiyun Xie 1,  Xueyan Zhang 2,  Ailin Tao 1,  Jie Yan 3
Affiliations

Affiliations

  • 1 The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou 510260, China.
  • 2 The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou 510260, China; School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.
  • 3 The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou 510260, China. Electronic address: [email protected].
PMID: 36470578 DOI: 10.1016/j.bbadis.2022.166613
Abstract

Pseudomonas aeruginosa induced acute lung injury is such a serious risk to public health, but the pathological regulation remains unclear. Here, we reported that PA mediated epithelial Necroptosis plays an important role in pathological process. Pharmacological and genomic ablation of Necroptosis signaling ameliorate PA mediated ALI and pulmonary inflammation. Our results further proved NLRP3 inflammasome to involve in the process. Mechanism investigation revealed the cross-talking between inflammasome activation and Necroptosis that MLKL-dependent Necroptosis signaling promotes the change of mitochondrial membrane potential for the release of Reactive Oxygen Species (ROS), which is the important trigger for functional inflammasome activation. Furthermore, antioxidants such as Mito-TEMPO was confirmed to significantly restrain inflammasome activation in epithelium, resulting in a reduction in PA induced pulmonary inflammation. Taken together, our findings revealed that necroptosis-triggered NLRP3 inflammasome in epithelium plays a crucial role in PA mediated injury, which could be a potential therapeutic target for pulmonary inflammation.

Keywords

Acute lung injury; Inflammasome; Mito-TEMPO; Necroptosis; Pseudomonas aeruginosa.

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