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AICAR was administered 6\u2005h post exposure (10\u2005mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      , intraperitoneal). We assessed survival, indices of lung injury, high mobility group box 1 (HMGB1) in the plasma, HO-1 levels in lung tissues and phosphorylation of AMPK and its upstream liver kinase B1 (LKB1). Rat alveolar type II epithelial (L2) cells and human club-like epithelial (H441) cells were also exposed to Br\n                      <jats:sub>2<\/jats:sub>\n                      (100\u2005ppm for 10\u2005min). After 24\u2005h we measured apoptosis and necrosis, AMPK and LKB1 phosphorylation, and HO-1 expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      There was a marked downregulation of phosphorylated AMPK and LKB1 in lung tissues and in L2 and H441 cells post exposure. AICAR increased survival in C57BL\/6 but not in HO-1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice. In WT mice, AICAR decreased lung injury and restored phosphorylated AMPK and phosphorylated LKB1 to control levels and increased HO-1 levels in both lung tissues and cells exposed to Br\n                      <jats:sub>2<\/jats:sub>\n                      . Treatment of L2 and H441 cells with small interfering RNAs against nuclear factor erythroid 2-related factor 2 or HO-1 abrogated the protective effects of AICAR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data indicate that the primary mechanism for the protective action of AICAR in toxic gas injury is the upregulation of lung HO-1 levels.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1183\/13993003.03694-2020","type":"journal-article","created":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T11:16:17Z","timestamp":1622200577000},"page":"2003694","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":40,"title":["AICAR decreases acute lung injury by phosphorylating AMPK and upregulating heme oxygenase-1"],"prefix":"10.1183","volume":"58","author":[{"given":"Israr","family":"Ahmad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Molyvdas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Yuan","family":"Jian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amie M.","family":"Traylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huachun","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6999-7633","authenticated-orcid":false,"given":"Gang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weifeng","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupam","family":"Agarwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6200-3851","authenticated-orcid":false,"given":"Tamas","family":"Jilling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurabh","family":"Aggarwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadis","family":"Matalon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2021,5,28]]},"reference":[{"key":"2024102102295898000_58.6.2003694.1","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1513\/AnnalsATS.201704-297WS","article-title":"An Official American Thoracic Society Workshop Report: chemical inhalational disasters. 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