tetano
Editor, Senior Moderator
J Virol. 2011 Nov 9. [Epub ahead of print]
Epigenetic Changes Mediated by miR29 Activate Cyclooxygenase-2 and Interferon-λ1 Production during Viral Infection.
Fang J, Hao Q, Liu L, Li Y, Wu J, Huo X, Zhu Y.
Source
The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Abstract
Interferon (IFN)-λ1 and cyclooxygenase (COX)-2 were reported to play an important role in host antiviral defense. However, the mechanism by which IFN-λ1 and COX2 is activated and modulated during viral infection remains unclear. In this study, we found that expression of both circulating IFN-λ1 and COX2-derived PGE2 was coordinately elevated in a cohort of influenza patients compared to healthy individuals. Expression of IFN-λ1 was blocked by a selective COX2 inhibitor during influenza A virus infection in A549 human lung epithelial cells, but enhanced by overexpression of COX2, indicating that production of IFN-λ1 is COX2 dependent. COX2 was able to increase IFN-λ1 expression by promoting NF-κB binding to the enhancer in IFN-λ1 promoter. We found that Epigenetic changes activate COX2 expression and PGE2 accumulation during viral infection. The expression of DNA methyltransferase (DNMT) 3a and DNMT3b, but not DNMT1, was down-regulated following influenza A virus infection both in A549 cells and peripheral blood mononuclear cells (PBMCs). We showed that microRNA(miR)29 suppresses DNMT activity and thus induces expression of COX2 and PGE2. Furthermore, miR29 expression was elevated 50-fold in virally-infected A549 cells and 10-fold in PBMCs from influenza patients, compared to expression after mock infection of A549 cells or in healthy individuals, respectively. Activation of the protein kinase A signaling pathway and phosphorylation of CREB1 also contributed to COX2 expression. Collectively, our work defines a novel proinflammatory cascade in the control of influenza A virus infection.
PMID:
22072783
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22072783
Epigenetic Changes Mediated by miR29 Activate Cyclooxygenase-2 and Interferon-λ1 Production during Viral Infection.
Fang J, Hao Q, Liu L, Li Y, Wu J, Huo X, Zhu Y.
Source
The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Abstract
Interferon (IFN)-λ1 and cyclooxygenase (COX)-2 were reported to play an important role in host antiviral defense. However, the mechanism by which IFN-λ1 and COX2 is activated and modulated during viral infection remains unclear. In this study, we found that expression of both circulating IFN-λ1 and COX2-derived PGE2 was coordinately elevated in a cohort of influenza patients compared to healthy individuals. Expression of IFN-λ1 was blocked by a selective COX2 inhibitor during influenza A virus infection in A549 human lung epithelial cells, but enhanced by overexpression of COX2, indicating that production of IFN-λ1 is COX2 dependent. COX2 was able to increase IFN-λ1 expression by promoting NF-κB binding to the enhancer in IFN-λ1 promoter. We found that Epigenetic changes activate COX2 expression and PGE2 accumulation during viral infection. The expression of DNA methyltransferase (DNMT) 3a and DNMT3b, but not DNMT1, was down-regulated following influenza A virus infection both in A549 cells and peripheral blood mononuclear cells (PBMCs). We showed that microRNA(miR)29 suppresses DNMT activity and thus induces expression of COX2 and PGE2. Furthermore, miR29 expression was elevated 50-fold in virally-infected A549 cells and 10-fold in PBMCs from influenza patients, compared to expression after mock infection of A549 cells or in healthy individuals, respectively. Activation of the protein kinase A signaling pathway and phosphorylation of CREB1 also contributed to COX2 expression. Collectively, our work defines a novel proinflammatory cascade in the control of influenza A virus infection.
PMID:
22072783
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22072783