Persistent Link:
http://hdl.handle.net/10150/282844
Title:
Glucocorticoid regulation of GM-CSF in bronchial epithelial cells
Author:
Adkins, Karissa Kathleen, 1971-
Issue Date:
1998
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Inflammation plays a central role in the pathogenesis of asthma. Glucocorticoids are first line antiinflammatory therapy in the treatment of asthma and are effective inhibitors of inflammatory cytokines. Clinical data demonstrate that granulocyte-macrophage colony-stimulating factor (GM-CSF) production by airway epithelial cells may be an important target of inhaled glucocorticoid therapy. In this study, the regulatory mechanisms of GM-CSF expression by interleukin-1β (IL-1β) and the synthetic glucocorticoid dexamethasone (DEX) were examined in the BEAS-2B human bronchial epithelial cell line. It is hypothesized that glucocorticoids inhibit GM-CSF production in these cells through transcriptional mechanisms involving induction of the NF-κB inhibitory protein, IκB-α. Treatment of the BEAS-2B cells with IL-1β induced GM-CSF protein and mRNA levels, and further investigation showed this induction was mediated through transcriptional mechanisms. DEX treatment of BEAS-2B cells inhibited IL-1β-induced GM-CSF protein and mRNA production. GM-CSF mRNA was rapidly degraded in these cells, and DEX treatment did not significantly affect this decay rate. These data suggest that dexamethasone repression of GM-CSF expression is mediated predominantly through transcriptional mechanisms. This study then examined expression of IκB-α in the BEAS-2B cells as a possible mechanism of glucocorticoid repression of GM-CSF. IκB-α RNA levels were minimally induced by DEX in these cells, but this did not result in concurrent induction of IκB-α protein. Additional analysis showed that DEX treatment of BEAS-2B cells did not prevent nuclear translocation of the NF-κB subunit p65, or IL-1β-induced degradation of IκB-α protein. From these data, this study concludes that induction of IκB-α is not a significant mechanism of glucocorticoid-mediated repression of GM-CSF in the BEAS-2B cells.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Biology, Cell.; Health Sciences, Pharmacology.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Pharmacology and Toxicology
Degree Grantor:
University of Arizona
Advisor:
Bloom, John W.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleGlucocorticoid regulation of GM-CSF in bronchial epithelial cellsen_US
dc.creatorAdkins, Karissa Kathleen, 1971-en_US
dc.contributor.authorAdkins, Karissa Kathleen, 1971-en_US
dc.date.issued1998en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractInflammation plays a central role in the pathogenesis of asthma. Glucocorticoids are first line antiinflammatory therapy in the treatment of asthma and are effective inhibitors of inflammatory cytokines. Clinical data demonstrate that granulocyte-macrophage colony-stimulating factor (GM-CSF) production by airway epithelial cells may be an important target of inhaled glucocorticoid therapy. In this study, the regulatory mechanisms of GM-CSF expression by interleukin-1β (IL-1β) and the synthetic glucocorticoid dexamethasone (DEX) were examined in the BEAS-2B human bronchial epithelial cell line. It is hypothesized that glucocorticoids inhibit GM-CSF production in these cells through transcriptional mechanisms involving induction of the NF-κB inhibitory protein, IκB-α. Treatment of the BEAS-2B cells with IL-1β induced GM-CSF protein and mRNA levels, and further investigation showed this induction was mediated through transcriptional mechanisms. DEX treatment of BEAS-2B cells inhibited IL-1β-induced GM-CSF protein and mRNA production. GM-CSF mRNA was rapidly degraded in these cells, and DEX treatment did not significantly affect this decay rate. These data suggest that dexamethasone repression of GM-CSF expression is mediated predominantly through transcriptional mechanisms. This study then examined expression of IκB-α in the BEAS-2B cells as a possible mechanism of glucocorticoid repression of GM-CSF. IκB-α RNA levels were minimally induced by DEX in these cells, but this did not result in concurrent induction of IκB-α protein. Additional analysis showed that DEX treatment of BEAS-2B cells did not prevent nuclear translocation of the NF-κB subunit p65, or IL-1β-induced degradation of IκB-α protein. From these data, this study concludes that induction of IκB-α is not a significant mechanism of glucocorticoid-mediated repression of GM-CSF in the BEAS-2B cells.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectBiology, Cell.en_US
dc.subjectHealth Sciences, Pharmacology.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplinePharmacology and Toxicologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorBloom, John W.en_US
dc.identifier.proquest9912152en_US
dc.identifier.bibrecord.b39124939en_US
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