title: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Debrecen, Hungary; Paprika Bioanalytics Bt, Debrecen, Hungary.
authors.forename: Johanna
authors.initials: J
authors.lastname: Mihály
authors.forename: Janine
authors.initials: J
authors.lastname: Gericke
authors.forename: Dániel
authors.initials: D
authors.lastname: Törőcsik
authors.forename: Krisztián
authors.initials: K
authors.lastname: Gáspár
authors.forename: Andrea
authors.initials: A
authors.lastname: Szegedi
authors.forename: Ralph
authors.initials: R
authors.lastname: Rühl
mesh_terms: D000293:Adolescent; D000328:Adult; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000201:enzymology*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D008297:Male; D018055:Receptors, Eicosanoid / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D055815:Young Adult
chemical_list: D005231:Fatty Acids, Unsaturated; D018055:Receptors, Eicosanoid; D001092:Arachidonate 12-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human
keywords: Atopic dermatitis; Cyclooxygenase pathway; Lipoxygenese pathway; PBMC