https://scholars.lib.ntu.edu.tw/handle/123456789/416756
標題: | Galectin-3 Enhances Avian H5N1 Influenza A Virus-Induced Pulmonary Inflammation by Promoting NLRP3 Inflammasome Activation | 作者: | Chen, Yu-Jung Wang, Sheng-Fan Weng, I-Chun Hong, Ming-Hsiang Lo, Tzu-Han Jan, Jia-Tsrong LI-CHUNG HSU Chen, Huan-Yuan Liu, Fu-Tong |
公開日期: | 2018 | 出版社: | ELSEVIER SCIENCE INC | 卷: | 188 | 期: | 4 | 起(迄)頁: | 1031 | 來源出版物: | The American journal of pathology | 摘要: | Highly pathogenic avian influenza A H5N1 virus causes pneumonia and acute respiratory distress syndrome in humans. Virus-induced excessive inflammatory response contributes to severe disease and high mortality rates. Galectin-3, a β-galactoside-binding protein widely distributed in immune and epithelial cells, regulates various immune functions and modulates microbial infections. Here, we describe galectin-3 up-regulation in mouse lung tissue after challenges with the H5N1 influenza virus. We investigated the effects of endogenous galectin-3 on H5N1 infection and found that survival of galectin-3 knockout (Gal-3KO) mice was comparable with wild-type (WT) mice after infections. Compared with infected WT mice, infected Gal-3KO mice exhibited less inflammation in the lungs and reduced IL-1β levels in bronchoalveolar lavage fluid. In addition, the bone marrow-derived macrophages (BMMs) from Gal-3KO mice exhibited reduced oligomerization of apoptosis-associated speck-like proteins containing caspase-associated recruitment domains and secreted less IL-1β compared with BMMs from WT mice. However, similar levels of the inflammasome component of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) were observed in two genotypes of BMMs. Co-immunoprecipitation data indicated galectin-3 and NLRP3 interaction in BMMs infected with H5N1. An association was also observed between galectin-3 and NLRP3/apoptosis-associated speck-like proteins containing caspase-associated recruitment domain complex. Combined, our results suggest that endogenous galectin-3 enhances the effects of H5N1 infection by promoting host inflammatory responses and regulating IL-1β production by macrophages via interaction with NLRP3. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85042213651&doi=10.1016%2fj.ajpath.2017.12.014&partnerID=40&md5=06c63c17f73282258ae6b924663ba4eb https://scholars.lib.ntu.edu.tw/handle/123456789/416756 |
ISSN: | 0002-9440 | DOI: | 10.1016/j.ajpath.2017.12.014 | SDG/關鍵字: | caspase; cryopyrin; galectin 3; inflammasome; interleukin 1beta; caspase recruitment domain signaling protein; cryopyrin; galectin 3; interleukin 1beta; Pycard protein, mouse; animal cell; animal tissue; apoptosis; Article; bone marrow derived macrophage; bronchoalveolar lavage fluid; controlled study; disease association; female; genotype; immunoprecipitation; Influenza A virus (H5N1); knockout mouse; lung parenchyma; mouse; nonhuman; oligomerization; pneumonia; priority journal; protein interaction; upregulation; wild type; animal; bird; C57BL mouse; dog; HEK293 cell line; human; Influenza A virus (H5N1); lung; macrophage; MDCK cell line; metabolism; orthomyxovirus infection; pathology; physiology; pneumonia; pyroptosis; survival analysis; virology; Animals; Birds; CARD Signaling Adaptor Proteins; Dogs; Galectin 3; HEK293 Cells; Humans; Influenza A Virus, H5N1 Subtype; Interleukin-1beta; Lung; Macrophages; Madin Darby Canine Kidney Cells; Mice, Inbred C57BL; Mice, Knockout; NLR Family, Pyrin Domain-Containing 3 Protein; Orthomyxoviridae Infections; Pneumonia; Pyroptosis; Survival Analysis; Up-Regulation |
顯示於: | 分子醫學研究所 |
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