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Eur J Immunol. 2016 Jul;46(7):1737-51. doi: 10.1002/eji.201546216. Epub 2016 May 12.

Oncostatin M overexpression induces skin inflammation but is not required in the mouse model of imiquimod-induced psoriasis-like inflammation.

Author information

1
Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC), EA 4331, Université de Poitiers, Poitiers, France.
2
Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
3
BioAlternatives, Gençay, France.
4
McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
5
INSERM UMR 957, Université de Nantes, Nantes, France.

Abstract

Oncostatin M (OSM) has been reported to be overexpressed in psoriasis skin lesions and to exert proinflammatory effects in vitro on human keratinocytes. Here, we report the proinflammatory role of OSM in vivo in a mouse model of skin inflammation induced by intradermal injection of murine OSM-encoding adenovirus (AdOSM) and compare with that induced by IL-6 injection. Here, we show that OSM potently regulates the expression of genes involved in skin inflammation and epidermal differentiation in murine primary keratinocytes. In vivo, intradermal injection of AdOSM in mouse ears provoked robust skin inflammation with epidermal thickening and keratinocyte proliferation, while minimal effect was observed after AdIL-6 injection. OSM overexpression in the skin increased the expression of the S100A8/9 antimicrobial peptides, CXCL3, CCL2, CCL5, CCL20, and Th1/Th2 cytokines, in correlation with neutrophil and macrophage infiltration. In contrast, OSM downregulated the expression of epidermal differentiation genes, such as cytokeratin-10 or filaggrin. Collectively, these results support the proinflammatory role of OSM when it is overexpressed in the skin. However, OSM expression was not required in the murine model of psoriasis induced by topical application of imiquimod, as demonstrated by the inflammatory phenotype of OSM-deficient mice or wild-type mice treated with anti-OSM antibodies.

KEYWORDS:

Imiquimod · Keratinocyte · Oncostatin M · Psoriasis · Skin inflammation

PMID:
27122058
DOI:
10.1002/eji.201546216
[Indexed for MEDLINE]
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