<p>Prostaglandin (PG) E<sub>2</sub> is an eicosanoid derived from the polyunsaturated twenty carbon fatty acid arachidonic acid (AA). PGE<sub>2</sub> has physiological as well as pathophysiological functions and is known to be a key mediator of inflammatory responses. Formation of PGE<sub>2</sub> is dependent upon the activities of three specific enzymes involved in the AA cascade; phospholipase A<sub>2</sub> (PLA<sub>2</sub>), cyclooxygenase (COX) and PGE synthase (PGEs). Although the research within this field has been intense for decades, the regulatory mechanisms concerning the PGE<sub>2</sub> synthesising enzymes are not completely established.</p><p>PGE<sub>2</sub> was investigated in human monocytes with or without lipopolysaccharide (LPS) pre-treatment followed by stimulation with calcium ionophore, opsonised zymosan or phorbol myristate acetate (PMA). Cytosolic PLA<sub>2</sub>a (cPLA<sub>2</sub>a) was shown to be pivotal for the mobilization of AA and subsequent formation of PGE<sub>2</sub>. Although COX-1 was constitutively expressed, monocytes required expression of COX-2 protein in order to convert the mobilized AA into PGH<sub>2</sub>. The conversion of PGH<sub>2</sub> to the final product PGE<sub>2</sub> was to a large extent due to the action of microsomal PGEs-1 (mPGEs-1). In addition, experiments with inhibitors of extracellular signal regulated kinase and p38 activation, indicated that phosphorylation of cPLA<sub>2</sub>α was markedly advantageous for the formation of PGE<sub>2</sub>.</p><p>Ellagic acid, a natural polyphenolic compound found in fruits and nuts, was shown to inhibit stimuli induced release of PGE<sub>2</sub> in human monocytes. The effect of ellagic acid was not due to a direct effect on the activities of the enzymes but rather to inhibition of the LPS-induced protein expression of COX-2, mPGEs-1 and cPLA<sub>2</sub>a.</p>
| Identifer | oai:union.ndltd.org:UPSALLA/oai:DiVA.org:kau-4638 |
| Date | January 2009 |
| Creators | Karlsson, Sofia |
| Publisher | Karlstad University, Faculty of Technology and Science |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Licentiate thesis, comprehensive summary, text |
| Relation | Karlstad University Studies, 1403-8099 ; 2009:43 |
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