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Studies of prostaglandin E<sub>2 </sub>formation<sub> </sub>in human monocytes

<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>

Identiferoai:union.ndltd.org:UPSALLA/oai:DiVA.org:kau-4638
Date January 2009
CreatorsKarlsson, Sofia
PublisherKarlstad University, Faculty of Technology and Science
Source SetsDiVA Archive at Upsalla University
LanguageEnglish
Detected LanguageEnglish
TypeLicentiate thesis, comprehensive summary, text
RelationKarlstad University Studies, 1403-8099 ; 2009:43

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