Prostaglandins (PGs) are lipid mediators derived from a cascade initiated by catalyzing arachidonic acid to PGH2 via the cyclooxygenases (COXs). Subsequently, downstream prostanoid synthases convert PGH2 into the biologically active PGs, which are potent mediators of pain and inflammation. Membrane prostaglandin E2 synthase-1 (mPGES-1) is a terminal prostaglandin synthase that isomerizes PGH2 into PGE2. Studies have shown that COX-2 and mPGES-1 are induced following pro-inflammatory stimuli in cell lines and tissues. The focus of this thesis was to better understand the role of mPGES-1 in inflammation, using rat adjuvant-induced arthritis as a model. Our study showed that mPGES-1 followed a similar induction profile as COX-2 by RNA and protein analysis, implying that mPGES-1 is the major terminal PGES enzyme downstream of COX-2 that plays a role in the inflamed rat paws. Immunofluorescence studies also revealed the induction of mPGES-1 along with COX-2, 3 days post-adjuvant treatment. These findings suggest that mPGES-1 may constitute a target for the treatment joint inflammation.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.80874 |
| Date | January 2003 |
| Creators | Sirinyan, Mirna |
| Contributors | Mancini, Joseph A. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Pharmacology & Therapeutics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002031520, proquestno: AAIMQ98739, Theses scanned by UMI/ProQuest. |
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