IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes

The Journal of Immunology, 174(6):3695-702

BONIFACE K., BERNARD FX., GARCIA M., GURNEY AL., LECRON JC. and MOREL F. (2005)

Laboratoire Cytokines et Inflammation, UPRES EA 3806, Pôle Biologie Santé, Université de Poitiers, France.
Bioalternatives, Gençay, France.

Abstract

IL-22 belongs to a family of cytokines structurally related to IL-10, including IL-19, IL-20, IL-24, and IL-26. In contrast to IL-10, IL-22 has proinflammatory activities. IL-22 signals through a class II cytokine receptor composed of an IL-22-binding chain, IL-22RA1, and the IL-10RB subunit, which is shared with the IL-10R.
In the present study, we show that short-term cultured human epidermal keratinocytes express a functional IL-22R but no IL-10R. Accordingly, IL-22 but not IL-10 induces STAT3 activation in keratinocytes. Using a cDNA array screening approach, real-time RT-PCR, and Western blot analysis, we demonstrate that IL-22 up-regulates, in a dose-dependent manner, the expression of S100A7, S100A8, S100A9, a group of proinflammatory molecules belonging to the S100 family of calcium-binding proteins, as well as the matrix metalloproteinase 3, the platelet-derived growth factor A, and the CXCL5 chemokine. In addition, IL-22 induces keratinocyte migration in an in vitro injury model and down-regulates the expression of at least seven genes associated with keratinocyte differentiation.
Finally, we show that IL-22 strongly induces hyperplasia of reconstituted human epidermis. Taken together, these results suggest that IL-22 plays an important role in skin inflammatory processes and wound healing.

© 2005 by The American Association of Immunologists.

KEYWORDS: IL-22; Keratinocyte; Migration

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