dc.date.accessioned | 2018-02-23T14:46:36Z | |
dc.date.available | 2018-02-23T14:46:36Z | |
dc.date.created | 2017-12-13T19:57:48Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Zago, Michela Sheridan, Jared A Traboulsi, Hussein Hecht, Emelia Zhang, Yelu Guerrina, Necola Matthews, Jason Nair, Parameswaran Eidelman, David H Hamid, Qutayba Baglole, Carolyn J. . Low levels of the AhR in chronic obstructive pulmonary disease (COPD)-derived lung cells increases COX-2 protein by altering mRNA stability. PLoS ONE. 2017, 12(7) | |
dc.identifier.uri | http://hdl.handle.net/10852/60376 | |
dc.description.abstract | Heightened inflammation, including expression of COX-2, is associated with chronic obstructive pulmonary disease (COPD) pathogenesis. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is reduced in COPD-derived lung fibroblasts. The AhR also suppresses COX-2 in response to cigarette smoke, the main risk factor for COPD, by destabilizing the Cox-2 transcript by mechanisms that may involve the regulation of microRNA (miRNA). Whether reduced AhR expression is responsible for heightened COX-2 in COPD is not known. Here, we investigated the expression of COX-2 as well as the expression of miR-146a, a miRNA known to regulate COX-2 levels, in primary lung fibroblasts derived from non-smokers (Normal) and smokers (At Risk) with and without COPD. To confirm the involvement of the AhR, AhR knock-down via siRNA in Normal lung fibroblasts and MLE-12 cells was employed as were A549-AhRko cells. Basal expression of COX-2 protein was higher in COPD lung fibroblasts compared to Normal or Smoker fibroblasts but there was no difference in Cox-2 mRNA. Knockdown of AhR in lung structural cells increased COX-2 protein by stabilizing the Cox-2 transcript. There was less induction of miR-146a in COPD-derived lung fibroblasts but this was not due to the AhR. Instead, we found that RelB, an NF-κB protein, was required for transcriptional induction of both Cox-2 and miR-146a. Therefore, we conclude that the AhR controls COX-2 protein via mRNA stability by a mechanism independent of miR-146a. Low levels of the AhR may therefore contribute to the heightened inflammation common in COPD patients. | en_US |
dc.language | EN | |
dc.publisher | Public Library of Science (PLoS) | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | Low levels of the AhR in chronic obstructive pulmonary disease (COPD)-derived lung cells increases COX-2 protein by altering mRNA stability | en_US |
dc.type | Journal article | en_US |
dc.creator.author | Zago, Michela | |
dc.creator.author | Sheridan, Jared A | |
dc.creator.author | Traboulsi, Hussein | |
dc.creator.author | Hecht, Emelia | |
dc.creator.author | Zhang, Yelu | |
dc.creator.author | Guerrina, Necola | |
dc.creator.author | Matthews, Jason | |
dc.creator.author | Nair, Parameswaran | |
dc.creator.author | Eidelman, David H | |
dc.creator.author | Hamid, Qutayba | |
dc.creator.author | Baglole, Carolyn J. | |
cristin.unitcode | 185,51,13,46 | |
cristin.unitname | Molekylær toksikologi | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 1527026 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=PLoS ONE&rft.volume=12&rft.spage=&rft.date=2017 | |
dc.identifier.jtitle | PLoS ONE | |
dc.identifier.volume | 12 | |
dc.identifier.issue | 7 | |
dc.identifier.doi | http://dx.doi.org/10.1371/journal.pone.0180881 | |
dc.identifier.urn | URN:NBN:no-63009 | |
dc.type.document | Tidsskriftartikkel | en_US |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 1932-6203 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/60376/4/journal.pone.0180881.pdf | |
dc.type.version | PublishedVersion | |