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The mice and MH\u2010S cells were administrated with lipopolysaccharide (LPS) to evoke the lung injury in\u00a0vivo and in\u00a0vitro. The role and mechanism of ANGPTL was investigated by haematoxylin\u2013eosin, measurement of wet\/dry ratio, cell count, terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling, reverse transcription quantitative polymerase chain reaction, immunofluorescence, enzyme\u2010linked immunosorbent assay, detection of autophagic flux and western blot assays. The level of ANGPTL2 was upregulated in lung injury. Knockout of ANGPTL2 alleviated LPS\u2010induced pathological symptoms, reduced pulmonary wet\/dry weight ratio, the numbers of total cells and neutrophils in BALF, apoptosis rate and the release of pro\u2010inflammatory mediators, and modulated polarization of alveolar macrophages in mice. Knockdown of ANGPTL2 downregulated the level of pyroptosis indicators, and elevated the level of autophagy in LPS\u2010induced MH\u2010S cells. Besides, downregulation of ANGPTL2 reversed the LPS\u2010induced the expression of leukocyte immunoglobulin (Ig)\u2010like receptor B2 (LILRB2) and triggering receptor expressed on myeloid cells 2 (TREM2), which was reversed by the overexpression of LILRB2. Importantly, knockdown of TREM2 reversed the levels of autophagy\u2010 and pyroptosis\u2010involved proteins, and the contents of pro\u2010inflammatory factors in LPS\u2010induced MH\u2010S cells transfected with si ANGPTL2, which was further inverted with the treatment of rapamycin. Therefore, ANGPTL2 silencing enhanced autophagy to alleviate alveolar macrophage pyroptosis via reducing LILRB2\u2010mediated inhibition of TREM2.<\/jats:p>","DOI":"10.1111\/jcmm.18280","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T14:24:55Z","timestamp":1715955895000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["ANGPTL2 knockdown induces autophagy to relieve alveolar macrophage pyroptosis by reducing LILRB2\u2010mediated inhibition of TREM2"],"prefix":"10.1111","volume":"28","author":[{"given":"Fan","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine The Affiliated Hospital of Southwest Medical University  Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine The Affiliated Hospital of Southwest Medical University  Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine The Affiliated Hospital of Southwest Medical University  Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingchun","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine The Affiliated Hospital of Southwest Medical University  Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangxi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine The Affiliated Hospital of Southwest Medical University  Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youwei","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine The Affiliated Hospital of Southwest Medical University  Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4324-4046","authenticated-orcid":false,"given":"Lu","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Thyroid Surgery The Affiliated Hospital of Southwest Medical University  Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-018-2051-8"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.124061"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0291"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13613-019-0619-3"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222010933"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.4187\/respcare.05752"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-020-01378-2"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiab044"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.F305"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3600"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01777"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2014.00004"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1159\/000100493"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.08.003"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.01.052"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090865"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.113.000201"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/1096385"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.05.186"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.160.7.3096"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-020-01406-7"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-022-00550-y"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.6.3520"},{"key":"e_1_2_10_25_1","unstructured":"National Research Council Committee for the Update of the Guide for the C Use of Laboratory A.The National Academies Collection: Reports funded by National Institutes of Health. 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