title: Involvement of IL-1 and oncostatin M in acanthosis associated with hypertensive leg ulcer.
abstract: Hypertensive leg ulcer (HLU) is an inflammatory disease characterized by intense pain, alteration of vascularization, and skin necrosis. The optimal treatment relies on surgical removal of necrotic tissues covered by a split-skin graft. We studied the histomorphology of the lesions and investigated the involvement of inflammatory cells and cytokines to further define the physiopathology of HLU. We report epidermis acanthosis and a preferential occlusion of the precapillary arterioles with infiltration of neutrophils, macrophages, and T lymphocytes in the dermis. OSM, IL-1β, and IL-6 were overexpressed in the ulcer, whereas the Th17-derived cytokines were not. In vitro, the addition of IL-1β and OSM promoted acanthosis and destructuring of reconstructed epidermis. Exogenous IL-1β and OSM synergistically induced epidermal acanthosis in mice. These data show that OSM and IL-1β are not only a biological characteristic signature of HLU, but these cytokines reflect a specific inflammatory state, directly involved in the pathogenesis. We suggest that anti-cytokine biotherapies could be an alternative strategy to surgery to treat HLU.
authors: LITEC, Pôle Biologie Santé, Poitiers University, Poitiers, France.
authors: Jean-Philippe
authors: JP
authors: Giot
authors: Isabelle
authors: I
authors: Paris
authors: Pierre
authors: P
authors: Levillain
authors: Vincent
authors: V
authors: Huguier
authors: Sandrine
authors: S
authors: Charreau
authors: Adrianna
authors: A
authors: Delwail
authors: Martine
authors: M
authors: Garcia
authors: Julien
authors: J
authors: Garnier
authors: François-Xavier
authors: FX
authors: Bernard
authors: Guy
authors: G
authors: Dagregorio
authors: Gérard
authors: G
authors: Guillet
authors: Franck
authors: F
authors: Morel
authors: Jean-Claude
authors: JC
authors: Lecron
authors: Laure
authors: L
authors: Favot
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D003251:Constriction, Pathologic / Q000150:complications / Q000473:pathology; D004817:Epidermis / Q000473:pathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D053550:Keratin-10 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D007871:Leg Ulcer / Q000150:complications* / Q000378:metabolism / Q000473:pathology*; D007962:Leukocytes / Q000473:pathology; D008297:Male; D008548:Melanosis / Q000150:complications* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000473:pathology; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D053683:Oncostatin M / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D019394:Ki-67 Antigen; D053683:Oncostatin M; D053550:Keratin-10