title: APN/CD13 is over-expressed by Psoriatic fibroblasts and is modulated by CGRP and IL-4 but not by retinoic acid treatment.
abstract: Psoriasis vulgaris is a common skin inflammatory disease characterized by recurrent flare episodes associated with scaly well-demarcated skin plaques. Skin biopsies from psoriatic patients with high PASI score (22.67 ± 8.67) and from HD were used to study APN/CD13. APN/CD13 is over-expressed in LP and nLP compare to HD skins and fibroblasts. This over-expression is positively correlated with specific enzymatic activity enhancement. However, discrepancies between APN/CD13 expression in LP and nLP prompt us to focus our study on APN/CD13 modulation. Calcitonin Gene Related Peptide (CGRP), a neuropeptide, positively modulated expression and activity of APN/CD13. CGRP consistently induced IL4 secretion, which is also involved in the increase of APN/CD13 expression and activity, which is significantly reversed using IL-4 blocking antibody. Surprisingly, retinoic acid altered the APN/CD13 enzymatic activity only in nLP fibroblasts without modification of APN/CD13 expression. APN/CD13 is over-expressed on psoriatic fibroblasts and exerted high level of activity compare to HD fibroblasts. Taken together, several factors such as CGRP and IL-4 acted on positive regulation of APN/CD13 expression and activity. This study highlighted the interest of APN/CD13 as a new potential target, which should be investigated in psoriasis.
authors.affiliation: INSERM, Université Paris Descartes, Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Gerbaud
authors.affiliation: Service de Biologie hormonale et métabolique, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Guibourdenche
authors.affiliation: Sup'Biotech, Villejuif, France.|CEA, Division of Prions and Related Diseases (SEPIA), Institute of Emerging Diseases and Innovative Therapies (iMETI), Fontenay-aux- Roses, France.
authors.forename: Rafika
authors.initials: R
authors.lastname: Jarray
authors.affiliation: Service de Biochimie, Hôpital Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est, Créteil, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Conti
authors.affiliation: Service d'Anatomie et Cytologie Pathologiques, CHU de Martinique, Hôpital Pierre Zobda Quitman, Fort-de-France Cedex, France.|Laboratory of Cellular and Molecular Basis of Normal Hematopoiesis and Hematological Disorders, INSERM UMR 1163, Paris, France.|Imagine Institute, Paris Descartes University-Sorbonne Paris Cité, Paris, France.|CNRS ERL 8254, Paris, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Palmic
authors.affiliation: Pathology Department and Reference Center for Rare Skin Diseases (MAGEC), Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Leclerc-Mercier
authors.affiliation: Laboratory of Cellular and Molecular Basis of Normal Hematopoiesis and Hematological Disorders, INSERM UMR 1163, Paris, France.|Imagine Institute, Paris Descartes University-Sorbonne Paris Cité, Paris, France.|CNRS ERL 8254, Paris, France.|Service de Pathologie, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Bruneau
authors.affiliation: Laboratory of Cellular and Molecular Basis of Normal Hematopoiesis and Hematological Disorders, INSERM UMR 1163, Paris, France.|Imagine Institute, Paris Descartes University-Sorbonne Paris Cité, Paris, France.|CNRS ERL 8254, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.affiliation: Laboratory of Cellular and Molecular Basis of Normal Hematopoiesis and Hematological Disorders, INSERM UMR 1163, Paris, France.|Imagine Institute, Paris Descartes University-Sorbonne Paris Cité, Paris, France.|CNRS ERL 8254, Paris, France.
authors.forename: Yves
authors.identifier: http://orcid.org/0000-0001-7746-5170
authors.initials: Y
authors.lastname: Lepelletier
authors.affiliation: Laboratory of Cellular and Molecular Basis of Normal Hematopoiesis and Hematological Disorders, INSERM UMR 1163, Paris, France.|Imagine Institute, Paris Descartes University-Sorbonne Paris Cité, Paris, France.|CNRS ERL 8254, Paris, France.|Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques (LCBPT), UMR 8601 CNRS, Université Paris Descartes, Sorbonne Paris Cité, UFR Biomédicale des Saints Pères, Paris, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Raynaud
mesh_terms: D000328:Adult; D000368:Aged; D018826:CD13 Antigens / Q000235:genetics / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D012867:Skin / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: C508598:IL4 protein, human; D015847:Interleukin-4; D014212:Tretinoin; D018826:CD13 Antigens; D015740:Calcitonin Gene-Related Peptide
keywords: CGRP; aminopeptidase-N; fibroblasts; interleukin-4; psoriasis