Abstract
Exposure to zinc-laden particulate matter in ambient and occupational settings has been associated with proinflammatory responses in the lung. Cyclooxygenase 2-derived eicosanoids are important modulators of airway inflammation. In this study, we characterized the transcriptional and posttranscriptional events that regulate COX-2 expression in a human bronchial epithelial cell line BEAS-2B exposed to Zn{sup 2+}. Zn{sup 2+} exposure resulted in pronounced increases in COX-2 mRNA and protein expression, which were prevented by pretreatment with the transcription inhibitor actinomycin D, implying the involvement of transcriptional regulation. This was supported by the observation of increased COX-2 promoter activity in Zn{sup 2+}-treated BEAS-2B cells. Mutation of the cAMP response element (CRE), but not the {kappa}B-binding sites in the COX-2 promoter markedly reduced COX-2 promoter activity induced by Zn{sup 2+}. Inhibition of NF{kappa}B activation did not block Zn{sup 2+}-induced COX-2 expression. Measurement of mRNA stability demonstrated that Zn{sup 2+} exposure impaired the degradation of COX-2 mRNA in BEAS-2B cells. This message stabilization effect of Zn{sup 2+} exposure was shown to be dependent on the integrity of the 3'-untranslated region found in the COX-2 transcript. Taken together, these data demonstrate that the CRE and mRNA stability regulates COX-2 expression induced in BEAS-2B cells exposed to extracellular
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Weidong, Wu;
[1]
Department of Pediatrics, University of North Carolina, Chapel Hill, NC (United States)], E-mail: Weidong_Wu@med.unc.edu;
Silbajoris, Robert A;
[2]
Dongsun, Cao;
[1]
Bromberg, Philip A;
[1]
Human Studies Division, National Health Effects and Environmental Effects Research Laboratory, Research Triangle Park, NC (United States)];
Qiao, Zhang;
[3]
Peden, David B;
[1]
Department of Pediatrics, University of North Carolina, Chapel Hill, NC (United States);
Human Studies Division, National Health Effects and Environmental Effects Research Laboratory, Research Triangle Park, NC (United States)];
Samet, James M
[2]
- Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina, Chapel Hill, NC (United States)
- Department of Medicine, University of North Carolina, Chapel Hill, NC (United States)
- College of Public Health, Zhengzhou University, Zhengzhou (China)
Citation Formats
Weidong, Wu, Department of Pediatrics, University of North Carolina, Chapel Hill, NC (United States)], E-mail: Weidong_Wu@med.unc.edu, Silbajoris, Robert A, Dongsun, Cao, Bromberg, Philip A, Human Studies Division, National Health Effects and Environmental Effects Research Laboratory, Research Triangle Park, NC (United States)], Qiao, Zhang, Peden, David B, Department of Pediatrics, University of North Carolina, Chapel Hill, NC (United States), Human Studies Division, National Health Effects and Environmental Effects Research Laboratory, Research Triangle Park, NC (United States)], and Samet, James M.
Regulation of cyclooxygenase-2 expression by cAMP response element and mRNA stability in a human airway epithelial cell line exposed to zinc.
United States: N. p.,
2008.
Web.
Weidong, Wu, Department of Pediatrics, University of North Carolina, Chapel Hill, NC (United States)], E-mail: Weidong_Wu@med.unc.edu, Silbajoris, Robert A, Dongsun, Cao, Bromberg, Philip A, Human Studies Division, National Health Effects and Environmental Effects Research Laboratory, Research Triangle Park, NC (United States)], Qiao, Zhang, Peden, David B, Department of Pediatrics, University of North Carolina, Chapel Hill, NC (United States), Human Studies Division, National Health Effects and Environmental Effects Research Laboratory, Research Triangle Park, NC (United States)], & Samet, James M.
Regulation of cyclooxygenase-2 expression by cAMP response element and mRNA stability in a human airway epithelial cell line exposed to zinc.
United States.
Weidong, Wu, Department of Pediatrics, University of North Carolina, Chapel Hill, NC (United States)], E-mail: Weidong_Wu@med.unc.edu, Silbajoris, Robert A, Dongsun, Cao, Bromberg, Philip A, Human Studies Division, National Health Effects and Environmental Effects Research Laboratory, Research Triangle Park, NC (United States)], Qiao, Zhang, Peden, David B, Department of Pediatrics, University of North Carolina, Chapel Hill, NC (United States), Human Studies Division, National Health Effects and Environmental Effects Research Laboratory, Research Triangle Park, NC (United States)], and Samet, James M.
2008.
"Regulation of cyclooxygenase-2 expression by cAMP response element and mRNA stability in a human airway epithelial cell line exposed to zinc."
United States.
@misc{etde_21140949,
title = {Regulation of cyclooxygenase-2 expression by cAMP response element and mRNA stability in a human airway epithelial cell line exposed to zinc}
author = {Weidong, Wu, Department of Pediatrics, University of North Carolina, Chapel Hill, NC (United States)], E-mail: Weidong_Wu@med.unc.edu, Silbajoris, Robert A, Dongsun, Cao, Bromberg, Philip A, Human Studies Division, National Health Effects and Environmental Effects Research Laboratory, Research Triangle Park, NC (United States)], Qiao, Zhang, Peden, David B, Department of Pediatrics, University of North Carolina, Chapel Hill, NC (United States), Human Studies Division, National Health Effects and Environmental Effects Research Laboratory, Research Triangle Park, NC (United States)], and Samet, James M}
abstractNote = {Exposure to zinc-laden particulate matter in ambient and occupational settings has been associated with proinflammatory responses in the lung. Cyclooxygenase 2-derived eicosanoids are important modulators of airway inflammation. In this study, we characterized the transcriptional and posttranscriptional events that regulate COX-2 expression in a human bronchial epithelial cell line BEAS-2B exposed to Zn{sup 2+}. Zn{sup 2+} exposure resulted in pronounced increases in COX-2 mRNA and protein expression, which were prevented by pretreatment with the transcription inhibitor actinomycin D, implying the involvement of transcriptional regulation. This was supported by the observation of increased COX-2 promoter activity in Zn{sup 2+}-treated BEAS-2B cells. Mutation of the cAMP response element (CRE), but not the {kappa}B-binding sites in the COX-2 promoter markedly reduced COX-2 promoter activity induced by Zn{sup 2+}. Inhibition of NF{kappa}B activation did not block Zn{sup 2+}-induced COX-2 expression. Measurement of mRNA stability demonstrated that Zn{sup 2+} exposure impaired the degradation of COX-2 mRNA in BEAS-2B cells. This message stabilization effect of Zn{sup 2+} exposure was shown to be dependent on the integrity of the 3'-untranslated region found in the COX-2 transcript. Taken together, these data demonstrate that the CRE and mRNA stability regulates COX-2 expression induced in BEAS-2B cells exposed to extracellular Zn{sup 2+}.}
journal = []
issue = {2}
volume = {231}
place = {United States}
year = {2008}
month = {Sep}
}
title = {Regulation of cyclooxygenase-2 expression by cAMP response element and mRNA stability in a human airway epithelial cell line exposed to zinc}
author = {Weidong, Wu, Department of Pediatrics, University of North Carolina, Chapel Hill, NC (United States)], E-mail: Weidong_Wu@med.unc.edu, Silbajoris, Robert A, Dongsun, Cao, Bromberg, Philip A, Human Studies Division, National Health Effects and Environmental Effects Research Laboratory, Research Triangle Park, NC (United States)], Qiao, Zhang, Peden, David B, Department of Pediatrics, University of North Carolina, Chapel Hill, NC (United States), Human Studies Division, National Health Effects and Environmental Effects Research Laboratory, Research Triangle Park, NC (United States)], and Samet, James M}
abstractNote = {Exposure to zinc-laden particulate matter in ambient and occupational settings has been associated with proinflammatory responses in the lung. Cyclooxygenase 2-derived eicosanoids are important modulators of airway inflammation. In this study, we characterized the transcriptional and posttranscriptional events that regulate COX-2 expression in a human bronchial epithelial cell line BEAS-2B exposed to Zn{sup 2+}. Zn{sup 2+} exposure resulted in pronounced increases in COX-2 mRNA and protein expression, which were prevented by pretreatment with the transcription inhibitor actinomycin D, implying the involvement of transcriptional regulation. This was supported by the observation of increased COX-2 promoter activity in Zn{sup 2+}-treated BEAS-2B cells. Mutation of the cAMP response element (CRE), but not the {kappa}B-binding sites in the COX-2 promoter markedly reduced COX-2 promoter activity induced by Zn{sup 2+}. Inhibition of NF{kappa}B activation did not block Zn{sup 2+}-induced COX-2 expression. Measurement of mRNA stability demonstrated that Zn{sup 2+} exposure impaired the degradation of COX-2 mRNA in BEAS-2B cells. This message stabilization effect of Zn{sup 2+} exposure was shown to be dependent on the integrity of the 3'-untranslated region found in the COX-2 transcript. Taken together, these data demonstrate that the CRE and mRNA stability regulates COX-2 expression induced in BEAS-2B cells exposed to extracellular Zn{sup 2+}.}
journal = []
issue = {2}
volume = {231}
place = {United States}
year = {2008}
month = {Sep}
}