title: Anti-Inflammatory Action of Keratinocyte-Derived Vaspin: Relevance for the Pathogenesis of Psoriasis.
abstract: Impaired cross talk between keratinocytes (KCs) and immune cells is believed to contribute to the pathogenesis of chronic inflammatory skin diseases, such as psoriasis. We have previously identified KCs as a rich source of the serpin protease inhibitor vaspin (serpinA12), originally described as an adipokine in adipose tissue. Herein, we studied whether dysregulated vaspin expression in KCs contributes to the pathogenesis of psoriasis. We found vaspin expression to be closely associated to epidermal differentiation, with low levels in proliferating KCs and high levels in differentiated cells. Consistently, in human psoriasis and in a mouse model of a psoriasis-like skin inflammation, epidermal vaspin expression was significantly down-regulated. Down-regulation of vaspin in KCs resulted in decreased expression of differentiation-associated genes and up-regulation of interferon-inducible and inflammation-associated psoriasis signature genes. Vaspin was also shown to modulate the communication between KCs and inflammatory cells under co-culture conditions. A decrease in vaspin expression in KCs stimulated the secretion of tumor necrosis factor-α, IL-1β, IL-6, IL-8, and monocyte chemoattractant protein-1 by co-cultured dendritic cells, macrophages, monocytes, and neutrophils. Consequently, the application of vaspin inhibited myeloid cell infiltration in a mouse model of a psoriasis-like skin inflammation. In conclusion, vaspin expression by maturing KCs modulates cutaneous immune responses and may be involved in the pathogenesis of psoriasis.
authors.affiliation: Department of Dermatology, Venerology, and Allergology, Medical Faculty, Leipzig University, Leipzig, Germany. Electronic address: anja.saalbach@medizin.uni-leipzig.de.
authors.forename: Anja
authors.initials: A
authors.lastname: Saalbach
authors.affiliation: Department of Dermatology, Venerology, and Allergology, Medical Faculty, Leipzig University, Leipzig, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Tremel
authors.affiliation: Department of Dermatology, Venerology, and Allergology, Medical Faculty, Leipzig University, Leipzig, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Herbert
authors.affiliation: Department of Dermatology, Venerology, and Allergology, Medical Faculty, Leipzig University, Leipzig, Germany; Integrated Research and Treatment Center, Adiposity Diseases Leipzig, Leipzig University, Leipzig, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schwede
authors.affiliation: Department of Dermatology, Venerology, and Allergology, Medical Faculty, Leipzig University, Leipzig, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Wandel
authors.affiliation: Department of Dermatology, Venerology, and Allergology, Medical Faculty, Leipzig University, Leipzig, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Schirmer
authors.affiliation: Department of Dermatology, Venerology, and Allergology, Medical Faculty, Leipzig University, Leipzig, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Anderegg
authors.affiliation: Institute of Biochemistry, Translational Centre for Regenerative Medicine, Institute of Biology, Leipzig University, Leipzig, Germany.
authors.forename: Annette G
authors.initials: AG
authors.lastname: Beck-Sickinger
authors.affiliation: Institute of Biochemistry, Translational Centre for Regenerative Medicine, Institute of Biology, Leipzig University, Leipzig, Germany.
authors.forename: John T
authors.initials: JT
authors.lastname: Heiker
authors.affiliation: Institute of Biochemistry, Translational Centre for Regenerative Medicine, Institute of Biology, Leipzig University, Leipzig, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Schultz
authors.affiliation: Division of Cell and Developmental Biology, Translational Centre for Regenerative Medicine, Institute of Biology, Leipzig University, Leipzig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Magin
authors.affiliation: Department of Dermatology, Venerology, and Allergology, Medical Faculty, Leipzig University, Leipzig, Germany.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Simon
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000276:immunology*; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D015603:Keratinocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000276:immunology* / Q000473:pathology; D015843:Serpins / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; C507339:SERPINA12 protein, human; D015843:Serpins