tetano
Editor, Senior Moderator
Am J Respir Cell Mol Biol. 2011 Jul 28. [Epub ahead of print]
Influenza Induces ER Stress, Caspase-12- Dependent Apoptosis and JNK Mediated TGF-{beta} Release in Lung Epithelial Cells.
Roberson EC, Tully JE, Guala AS, Reiss JN, Godburn KE, Pociask DA, Alcorn JF, Riches DW, Dienz O, Janssen-Heininger YM, Anathy V.
Source
Pathology, University of Vermont, Burlington, Vermont, United States.
Abstract
Influenza A virus (IAV) infection is known to induce endoplasmic reticulum stress (ER stress), Fas dependent apoptosis, TGF-β production in a variety of cells. However, the relationship between these events in mouse primary tracheal epithelial cells (MTECS), which are considered to be one of the primary sites of IAV infection and replication, is unclear. We show that IAV infection induced ER stress marker ATF6 and ERp57, but not 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. Decrease of ERp57 attenuated IAV burden and decreased caspase-12 activation and apoptosis in epithelial cells. TGF-β production was enhanced in IAV infected MTECs as compared to THP or staurosporine (STS). IAV infection caused activation of c-jun N-terminal kinase (JNK). Further, IAV-induced TGF-β production required the presence of JNK1, findings that suggest a role for JNK1 in IAV-induced epithelial injury and subsequent TGF-β production. These novel findings suggest a potential mechanistic role for a distinct ER stress response induced by IAV, and a pro-fibrogenic/repair response in comparison to other pharmacological inducers of ER stress. These responses may also have a potential role in acute lung injury, fibro-proliferative acute respiratory distress syndrome, and recently identified H1N1- induced exacerbations of chronic obstructive pulmonary disease (1) and idiopathic pulmonary fibrosis (2).
PMID:
21799120
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21799120
Influenza Induces ER Stress, Caspase-12- Dependent Apoptosis and JNK Mediated TGF-{beta} Release in Lung Epithelial Cells.
Roberson EC, Tully JE, Guala AS, Reiss JN, Godburn KE, Pociask DA, Alcorn JF, Riches DW, Dienz O, Janssen-Heininger YM, Anathy V.
Source
Pathology, University of Vermont, Burlington, Vermont, United States.
Abstract
Influenza A virus (IAV) infection is known to induce endoplasmic reticulum stress (ER stress), Fas dependent apoptosis, TGF-β production in a variety of cells. However, the relationship between these events in mouse primary tracheal epithelial cells (MTECS), which are considered to be one of the primary sites of IAV infection and replication, is unclear. We show that IAV infection induced ER stress marker ATF6 and ERp57, but not 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. Decrease of ERp57 attenuated IAV burden and decreased caspase-12 activation and apoptosis in epithelial cells. TGF-β production was enhanced in IAV infected MTECs as compared to THP or staurosporine (STS). IAV infection caused activation of c-jun N-terminal kinase (JNK). Further, IAV-induced TGF-β production required the presence of JNK1, findings that suggest a role for JNK1 in IAV-induced epithelial injury and subsequent TGF-β production. These novel findings suggest a potential mechanistic role for a distinct ER stress response induced by IAV, and a pro-fibrogenic/repair response in comparison to other pharmacological inducers of ER stress. These responses may also have a potential role in acute lung injury, fibro-proliferative acute respiratory distress syndrome, and recently identified H1N1- induced exacerbations of chronic obstructive pulmonary disease (1) and idiopathic pulmonary fibrosis (2).
PMID:
21799120
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21799120