Low levels of the AhR in chronic obstructive pulmonary disease (COPD)-derived lung cells increases COX-2 protein by altering mRNA stability
Publication Date
July 27, 2017
Authors
Michela Zago, Jared A. Sheridan, Hussein Traboulsi, Emelia Hecht, et al
Volume
12
Issue
7
Pages
e0180881
DOI
https://dx.plos.org/10.1371/journal.pone.0180881
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0180881
Scopus
85026529897
Mendeley
http://www.mendeley.com/research/low-levels-ahr-chronic-obstructive-pulmonary-disease-copdderived-lung-cells-increases-cox2-protein-a
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Mendeley | Further Information

{"title"=>"Low levels of the AhR in chronic obstructive pulmonary disease (COPD)-derived lung cells increases COX-2 protein by altering mRNA stability", "type"=>"journal", "authors"=>[{"first_name"=>"Michela", "last_name"=>"Zago", "scopus_author_id"=>"34574026600"}, {"first_name"=>"Jared A.", "last_name"=>"Sheridan", "scopus_author_id"=>"36500414300"}, {"first_name"=>"Hussein", "last_name"=>"Traboulsi", "scopus_author_id"=>"57191803588"}, {"first_name"=>"Emelia", "last_name"=>"Hecht", "scopus_author_id"=>"56065758600"}, {"first_name"=>"Yelu", "last_name"=>"Zhang", "scopus_author_id"=>"57195253879"}, {"first_name"=>"Necola", "last_name"=>"Guerrina", "scopus_author_id"=>"57192988328"}, {"first_name"=>"Jason", "last_name"=>"Matthews", "scopus_author_id"=>"56820683900"}, {"first_name"=>"Parameswaran", "last_name"=>"Nair", "scopus_author_id"=>"7201717388"}, {"first_name"=>"David H.", "last_name"=>"Eidelman", "scopus_author_id"=>"7005951484"}, {"first_name"=>"Qutayba", "last_name"=>"Hamid", "scopus_author_id"=>"7102995930"}, {"first_name"=>"Carolyn J.", "last_name"=>"Baglole", "scopus_author_id"=>"57192993304"}], "year"=>2017, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "sgr"=>"85026529897", "doi"=>"10.1371/journal.pone.0180881", "pmid"=>"28749959", "scopus"=>"2-s2.0-85026529897", "pui"=>"617563324"}, "id"=>"8050bb53-a2ea-3645-9283-f7c6a2ada452", "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.", "link"=>"http://www.mendeley.com/research/low-levels-ahr-chronic-obstructive-pulmonary-disease-copdderived-lung-cells-increases-cox2-protein-a", "reader_count"=>1, "reader_count_by_academic_status"=>{"Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "reader_count_by_subdiscipline"=>{"Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "group_count"=>0}

Scopus | Further Information

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