title: β-casomorphin-7 alters μ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis.
abstract: Atopic dermatitis (AD) is a chronic inflammatory skin disease with heterogeneous clinical phenotypes reflecting genetic predisposition and exposure to environmental factors. Reactions to food may play a significant role especially in young children. Milk proteins are particularly strong allergens and are additional source of bioactive peptides including β-casomorphin-7 (BCM7, Tyr-Pro-Phe-Pro-Gly-Pro-Ile). BCM7 exerts its influence on nervous, digestive, and immune functions via the μ-opioid receptor (MOR). Proline dipeptidyl peptidase IV (DPPIV; EC 3.4.14.5) appears to be the primary degrading enzyme of BCM7. Moreover, DPPIV is known to restrict activity of proinflammatory peptides. BCM7 is considered to modulate an immune response by affecting MOR and DPPIV genes expression. In this study, we determined the MOR and DPPIV genes expression in children diagnosed with a severe form of AD. 40 healthy children and 62 children diagnosed with severe AD (AD score ≥60) were included in the study. Peripheral blood mononuclear cells (PBMCs) from the studied subjects were incubated with the peptide extracts of raw and hydrolysed cow milk with defined β-casein genotypes (A1A1, A2A2 and A1A2) and MOR and DPPIV genes expression was determined with real-time PCR. Incubation PBMCs with peptide extracts from cow milk caused an increase of the MOR gene expression (p<0.05; p<0.001) in AD children with a simultaneous decrease in the DPPIV gene expression (p<0.001). The obtained results supplement the knowledge on the BCM7 participation in AD etiology and provide an important diagnostic tool.
authors.affiliation: Chair of Biochemistry, Faculty of Biology and Biotechnology, University of Warmia and Mazury, Olsztyn, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Fiedorowicz
authors.affiliation: Department of Paediatrics, Gastroenterology and Allergology, Medical University of Białystok, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Kaczmarski
authors.affiliation: Chair of Biochemistry, Faculty of Biology and Biotechnology, University of Warmia and Mazury, Olsztyn, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Cieślińska
authors.affiliation: Chair of Biochemistry, Faculty of Biology and Biotechnology, University of Warmia and Mazury, Olsztyn, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Sienkiewicz-Szłapka
authors.affiliation: Chair of Biochemistry, Faculty of Biology and Biotechnology, University of Warmia and Mazury, Olsztyn, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Jarmołowska
authors.affiliation: The Regional Children's Specialized Hospital, Olsztyn, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Chwała
authors.affiliation: Chair of Biochemistry, Faculty of Biology and Biotechnology, University of Warmia and Mazury, Olsztyn, Poland. Electronic address: elzbieta.kostyra@uwm.edu.pl.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Kostyra
mesh_terms: D000293:Adolescent; D000485:Allergens / Q000187:drug effects; D000818:Animals; D002417:Cattle; D002648:Child; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018819:Dipeptidyl Peptidase 4 / Q000096:biosynthesis; D004723:Endorphins / Q000008:administration & dosage* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D016269:Milk Hypersensitivity / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008894:Milk Proteins / Q000009:adverse effects; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000096:biosynthesis
chemical_list: D000485:Allergens; D004723:Endorphins; D008894:Milk Proteins; D010446:Peptide Fragments; D017450:Receptors, Opioid, mu; C041128:beta-casomorphin 7; D018819:Dipeptidyl Peptidase 4
keywords: Atopic dermatitis; Cow milk; Milk allergy; Proline dipeptidyl peptidase IV; β-Casomorphin; μ-Opioid receptor