title: Oncostatin M secreted by skin infiltrating T lymphocytes is a potent keratinocyte activator involved in skin inflammation.
abstract: Cutaneous inflammatory diseases such as psoriasis vulgaris and atopic dermatitis are associated with altered keratinocyte function, as well as with a particular cytokine production profile of skin-infiltrating T lymphocytes. In this study we show that normal human epidermal keratinocytes express a functional type II oncostatin-M (OSM) receptor (OSMR) consisting of the gp130 and OSMRbeta components, but not the type I OSMR. The type II OSMR is expressed in skin lesions from both psoriatic patients and those with atopic dermatitis. Its ligand, OSM, induces via the recruitment of the STAT3 and MAP kinase pathways a gene expression profile in primary keratinocytes and in a reconstituted epidermis that is characteristic of proinflammatory and innate immune responses. Moreover, OSM is a potent stimulator of keratinocyte migration in vitro and increases the thickness of a reconstituted epidermis. OSM transcripts are enhanced in both psoriatic and atopic dermatitic skin as compared with healthy skin and mirror the enhanced production of OSM by T cells isolated from diseased lesions. Results from a microarray analysis comparing the gene-modulating effects of OSM with those of 33 different cytokines indicate that OSM is a potent keratinocyte activator similar to TNF-alpha, IL-1, IL-17, and IL-22 and that it acts in synergy with the latter cytokines in the induction of S100A7 and beta-defensin 2 expression, characteristic of psoriatic skin. Taken together, these results demonstrate that OSM and its receptor play an important role in cutaneous inflammatory responses in general and that the specific effects of OSM are associated with distinct inflammatory diseases depending on the cytokine environment.
authors: UPRES-EA 3806, Centre Hospitalier de l'Université de Poitiers, Poitiers, France.
authors: Katia
authors: K
authors: Boniface
authors: Caroline
authors: C
authors: Diveu
authors: Franck
authors: F
authors: Morel
authors: Nathalie
authors: N
authors: Pedretti
authors: Josy
authors: J
authors: Froger
authors: Elisa
authors: E
authors: Ravon
authors: Martine
authors: M
authors: Garcia
authors: Emilie
authors: E
authors: Venereau
authors: Laurence
authors: L
authors: Preisser
authors: Emmanuel
authors: E
authors: Guignouard
authors: Gérard
authors: G
authors: Guillet
authors: Guy
authors: G
authors: Dagregorio
authors: Jérôme
authors: J
authors: Pène
authors: Jean-Pierre
authors: JP
authors: Moles
authors: Hans
authors: H
authors: Yssel
authors: Sylvie
authors: S
authors: Chevalier
authors: François-Xavier
authors: FX
authors: Bernard
authors: Hugues
authors: H
authors: Gascan
authors: Jean-Claude
authors: JC
authors: Lecron
mesh_terms: D002465:Cell Movement; D002478:Cells, Cultured; D003872:Dermatitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D015603:Keratinocytes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D053683:Oncostatin M / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D053679:Receptors, Oncostatin M, Type II / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D053679:Receptors, Oncostatin M, Type II; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D053683:Oncostatin M; D020929:Mitogen-Activated Protein Kinase Kinases