Lipoxygenases (LOX) and cyclooxygenases (COX) are the main enzymes for poly-unsaturated fatty acid (PUFA) metabolism to highly bioactive prostaglandins, leukotrienes, thromboxanes and protectins. LOX and COX pathways are highly important for the regulation of pro- and anti-inflammatory active metabolite synthesis and metabolism in various inflammatory diseases like atopic diseases (AD). In this study using QRT-PCR, we found that in PBMCs the expression of 5-LOX, 12-LOX, 15-LOX and COX pathways and further enzymatic pathways like various leukotriene-hydoxylases, leukotriene-, prostaglandin-, and thromboxane-synthases as well as various of their membrane based receptors are mainly significantly down-regulated in AD-patients vs. healthy volunteers. In addition, using HPLC MS-MS we determined up to 19 different metabolites originating from eicosapentaenoic acid (EPA), docosapentaenoic acid (DHA) and arachidonic acid (AA) ranging from hydroxylated-PUFA derivatives and further bioactive derivatives like thromboxanes, leukotrienes, prostaglandins and protectins originating from LOX and COX metabolism. In PBMCs from AD-patients LOX and COX pathways were down-regulated. We conclude from this study, that in PBMCs from AD-patients in comparison to healthy volunteers, a systemic down-regulation of LOX- and COX-responses occurs to generally reduce eicosanoid/docosanoid synthesis during the current allergic inflammatory status.
Keywords: Atopic dermatitis; Cyclooxygenase pathway; Lipoxygenese pathway; PBMC.
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