Reduced lipoxygenase and cyclooxygenase mediated signaling in PBMC of atopic dermatitis patients

Abstract

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.