IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes.
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.
Boniface
Katia
K
Laboratoire Cytokines et Inflammation, UPRES EA 3806, Pôle Biologie Santé, Université de Poitiers, Poitiers, France.
Bernard
François-Xavier
FX
Garcia
Martine
M
Gurney
Austin L
AL
Lecron
Jean-Claude
JC
Morel
Franck
F
D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000235:genetics; D040501:Calgranulin A / Q000235:genetics; D040502:Calgranulin B / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D000097043:Interleukin-22
D002135:Calcium-Binding Proteins; D040501:Calgranulin A; D040502:Calgranulin B; D004247:DNA; D004268:DNA-Binding Proteins; D018836:Inflammation Mediators; D016753:Interleukin-10; D007378:Interleukins; D019278:Matrix Metalloproteinase 3; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D011994:Recombinant Proteins; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D000097043:Interleukin-22; C089242:S100A7 protein, human; C494086:STAT3 protein, human; C415369:interleukin-22 receptor