Involvement of IL-1 and Oncostatin M in acanthosis associated with hypertensive leg ulcer

The American Journal of Pathology, 182(3):806-18

GIOT JP., PARIS I., LEVILLAIN P., HUGUIER V., CHARREAU S., DELWAIL A., GARCIA M., BERNARD FX., DAGREGORIO G., GUILLET G., MOREL F., LECRON JC. and FAVOT L. (2013)

Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UPRES EA4331, Pôle Biologie Santé, Université de Poitiers, France.
CHU de Poitiers, France.
Bioalternatives, Gençay, France.

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.

© 2013 American Society for Investigative Pathology.

KEYWORDS: IL-1; Oncostatin M

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