{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:27:07Z","timestamp":1790389627156,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2012,5,1]],"date-time":"2012-05-01T00:00:00Z","timestamp":1335830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Influenza A virus (IAV) infection is known to induce endoplasmic reticulum (ER) stress, Fas-dependent apoptosis, and TGF-\u03b2 production in a variety of cells. However, the relationship between these events in murine primary tracheal epithelial cells (MTECS), which are considered one of the primary sites of IAV infection and replication, is unclear. We show that IAV infection induced ER stress marker activating transcription factor\u20136 and endoplasmic reticulum protein 57-kD (ERp57), but not C\/EBP homologous protein (CHOP). In contrast, the ER stress inducer thapsigargin (THP) increased CHOP. IAV infection activated caspases and apoptosis, independently of Fas and caspase-8, in MTECs. Instead, apoptosis was mediated by caspase-12. A decrease in ERp57 attenuated the IAV burden and decreased caspase-12 activation and apoptosis in epithelial cells. TGF-\u03b2 production was enhanced in IAV\u2013infected MTECs, compared with THP or staurosporine. IAV infection caused the activation of c-Jun N-terminal kinase (JNK). Furthermore, IAV-induced TGF-\u03b2 production required the presence of JNK1, a finding that suggests a role for JNK1 in IAV-induced epithelial injury and subsequent TGF-\u03b2 production. These novel findings suggest a potential mechanistic role for a distinct ER stress response induced by IAV, and a profibrogenic\/repair response in contrast to other pharmacological inducers of ER stress. These responses may also have a potential role in acute lung injury, fibroproliferative acute respiratory distress syndrome, and the recently identified H1N1 influenza\u2013induced exacerbations of chronic obstructive pulmonary disease (Wedzicha JA. Proc Am Thorac Soc 2004;1:115\u2013120) and idiopathic pulmonary fibrosis (Umeda Y, et al. Int Med 2010;49:2333\u20132336).<\/jats:p>","DOI":"10.1165\/rcmb.2010-0460oc","type":"journal-article","created":{"date-parts":[[2011,7,28]],"date-time":"2011-07-28T23:12:49Z","timestamp":1311894769000},"page":"573-581","source":"Crossref","is-referenced-by-count":115,"title":["Influenza Induces Endoplasmic Reticulum Stress, Caspase-12\u2013Dependent Apoptosis, and c-Jun N-Terminal Kinase\u2013Mediated Transforming Growth Factor\u2013\u03b2 Release in Lung Epithelial Cells"],"prefix":"10.1093","volume":"46","author":[{"given":"Elle C.","family":"Roberson","sequence":"first","affiliation":[{"name":"Department of Pathology"},{"name":"Honors College, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane E.","family":"Tully","sequence":"additional","affiliation":[{"name":"Department of Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy S.","family":"Guala","sequence":"additional","affiliation":[{"name":"Department of Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica N.","family":"Reiss","sequence":"additional","affiliation":[{"name":"Department of Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolyn E.","family":"Godburn","sequence":"additional","affiliation":[{"name":"Department of Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek A.","family":"Pociask","sequence":"additional","affiliation":[{"name":"Louisiana State University Health Science Center, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Alcorn","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W. H.","family":"Riches","sequence":"additional","affiliation":[{"name":"Program in Cell Biology, National Jewish Health, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Dienz","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Vermont, Burlington Vermont"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne M. 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