title: Allergen-induced dermatitis causes alterations in cutaneous retinoid-mediated signaling in mice.
abstract: Nuclear receptor-mediated signaling via RARs and PPARδ is involved in the regulation of skin homeostasis. Moreover, activation of both RAR and PPARδ was shown to alter skin inflammation. Endogenous all-trans retinoic acid (ATRA) can activate both receptors depending on specific transport proteins: Fabp5 initiates PPARδ signaling whereas Crabp2 promotes RAR signaling. Repetitive topical applications of ovalbumin (OVA) in combination with intraperitoneal injections of OVA or only intraperitoneal OVA applications were used to induce allergic dermatitis. In our mouse model, expression of IL-4, and Hbegf increased whereas expression of involucrin, Abca12 and Spink5 decreased in inflamed skin, demonstrating altered immune response and epidermal barrier homeostasis. Comprehensive gene expression analysis showed alterations of the cutaneous retinoid metabolism and retinoid-mediated signaling in allergic skin immune response. Notably, ATRA synthesis was increased as indicated by the elevated expression of retinaldehyde dehydrogenases and increased levels of ATRA. Consequently, the expression pattern of genes downstream to RAR was altered. Furthermore, the increased ratio of Fabp5 vs. Crabp2 may indicate an up-regulation of the PPARδ pathway in allergen-induced dermatitis in addition to the altered RAR signaling. Thus, our findings suggest that ATRA levels, RAR-mediated signaling and signaling involved in PPARδ pathways are mainly increased in allergen-induced dermatitis and may contribute to the development and/or maintenance of allergic skin diseases.
authors: Laboratory of Nutritional Bioactivation and Bioanalysis, Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary.
authors: Janine
authors: J
authors: Gericke
authors: Jan
authors: J
authors: Ittensohn
authors: Johanna
authors: J
authors: Mihály
authors: Sandrine
authors: S
authors: Dubrac
authors: Ralph
authors: R
authors: Rühl
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000276:immunology; D000485:Allergens / Q000009:adverse effects*; D000818:Animals; D003872:Dermatitis / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology; D010047:Ovalbumin / Q000009:adverse effects*; D047494:PPAR delta / Q000235:genetics* / Q000276:immunology; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology; D018168:Receptors, Retinoic Acid / Q000235:genetics* / Q000276:immunology; D000072482:Retinoic Acid Receptor alpha; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D015843:Serpins / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; C532573:Abca12 protein, mouse; D000485:Allergens; C082667:Fabp5 protein, mouse; D050556:Fatty Acid-Binding Proteins; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D047494:PPAR delta; D011498:Protein Precursors; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D015843:Serpins; C495972:Spink5 protein, mouse; C082928:retinoic acid binding protein II, cellular; D015847:Interleukin-4; D014212:Tretinoin; C032253:involucrin; D010047:Ovalbumin
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