1. IL-19 Is a Component of the Pathogenetic IL-23/IL-17 Cascade in Psoriasis.
- Author
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Witte, Ellen, Kokolakis, Georgios, Witte, Katrin, Philipp, Sandra, Doecke, Wolf-Dietrich, Babel, Nina, Wittig, Bianca M, Warszawska, Katarzyna, Kurek, Agata, Erdmann-Keding, Magdalena, Kunz, Stefanie, Asadullah, Khusru, Kadin, Marshall E, Volk, Hans-Dieter, Sterry, Wolfram, Wolk, Kerstin, and Sabat, Robert
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PSORIASIS , *CYTOKINES , *KERATINOCYTES , *CHEMOKINES , *TUMOR necrosis factors , *METALLOPROTEINASES , *NEUTROPHILS - Abstract
Psoriasis is a common chronic inflammatory disease with characteristic skin alterations and functions as a model of immune-mediated disorders. Cytokines have a key role in psoriasis pathogenesis. Here, we demonstrated that out of 30 individually quantified cytokines, IL-19 showed the strongest differential expression between psoriatic lesions and healthy skin. Cutaneous IL-19 overproduction was reflected by elevated IL-19 blood levels that correlated with psoriasis severity. Accordingly, anti-psoriatic therapies substantially reduced both cutaneous and systemic IL-19 levels. IL-19 production was induced in keratinocytes by IL-17A and was further amplified by tumor necrosis factor-α and IL-22. Among skin cells, keratinocytes were found to be important targets of IL-19. IL-19 alone, however, regulated only a few keratinocyte functions. While increasing the production of S100A7/8/9 and, to a moderate extent, also IL-1β, IL-20, chemokine C-X-C motif ligand 8, and matrix metalloproteinase 1, IL-19 had no clear influence on the differentiation, proliferation, or migration of these cells. Importantly, IL-19 amplified many IL-17A effects on keratinocytes, including the induction of β-defensins, IL-19, IL-23p19, and T helper type 17-cell- and neutrophil-attracting chemokines. In summary, IL-19 as a component of the IL-23/IL-17 axis strengthens the IL-17A action and might be a biomarker for the activity of this axis in chronic inflammatory disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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