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dc.contributor.advisorRogers, Thomas J., 1950-
dc.creatorHappel, Christine
dc.date.accessioned2020-10-26T19:19:15Z
dc.date.available2020-10-26T19:19:15Z
dc.date.issued2009
dc.identifier.other864884761
dc.identifier.urihttp://hdl.handle.net/20.500.12613/1390
dc.description.abstractOpioid receptor modulation of pro-inflammatory cytokine production is vital for host defense and the inflammatory response. Previous results have shown the mu-opioid receptor (MOR) selective agonist, DAMGO, has the capacity to increase the expression of the pro-inflammatory chemokines, CCL2/MCP-1, CCL5/RANTES and CXCL10/IP-10 in peripheral blood mononuclear cells (PBMCs). We have shown that MOR activation is able to induce the expression of TGF-β, and TGF-β appears to be required for induction of CCL5 following MOR activation. This work suggests a novel role for TGF-β in the inflammatory response. NF-κB is a transcription factor that plays a pivotal role in inflammation and the immune response. We have found that NF-kB inhibitors can prevent the MOR-induced activation of CCL2 and CCL5, and that the NF-kB subunit, p65, is phosphorylated at serine residues 311 and 536 in response to μ-opioid receptor activation. In vivo, DAMGO administration can induce binding of p. 65 to the enhancer region of the CCL2 promoter. Furthermore, we demonstrate that PKCζ is phosphorylated following DAMGO-induced MOR activation and, is essential for NF-kB activity as well as CCL2 expression and transcriptional activity. In conclusion, these data suggest a pro-inflammatory role for MOR which involves NF-κB activation and PKCζ as well as a novel role for TGF-β as a regulator of pro-inflammatory chemokines.
dc.format.extent241 pages
dc.language.isoeng
dc.publisherTemple University. Libraries
dc.relation.ispartofTheses and Dissertations
dc.rightsIN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available.
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectBiology, Microbiology
dc.subjectChemokines
dc.subjectNf-kappa B
dc.subjectOpioid
dc.subjectOpioid Receptor
dc.subjectPkc
dc.titleMolecular Basis for Mu-Opioid Regulation of Chemokine Gene Expression
dc.typeText
dc.type.genreThesis/Dissertation
dc.contributor.committeememberDhanasekaran, Danny
dc.contributor.committeememberLiebermann, Dan A., 1949-
dc.contributor.committeememberTsygankov, Alexander Y.
dc.contributor.committeememberReiss, Krzysztof
dc.description.departmentMolecular Biology and Genetics
dc.relation.doihttp://dx.doi.org/10.34944/dspace/1372
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.degreePh.D.
refterms.dateFOA2020-10-26T19:19:15Z


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