IL-17 and IL-22 enhance skin inflammation by stimulating the secretion of IL-1ß by keratinocytes via the ROS-NLRP3-caspase-1 pathway.
Int Immunol
; 24(3): 147-58, 2012 Mar.
Article
em En
| MEDLINE
| ID: mdl-22207130
ABSTRACT
BACKGROUND:
The pathogenesis of inflammatory skin disease involves the release of cytokines from keratinocytes, and one of these, IL-1ß, has been previously implicated in inflammatory skin disease. T(h)17 cells, a subset of T(h) cells involved in autoimmunity and inflammation, possess IL-1ß receptors and secrete cytokines such as IL-17 and IL-22 in response to IL-1ß stimulation. A mutation in the inflammasome protein NLRP3 (NACHT, LRR and PYD domains-containing protein 3) causes excess production of IL-1ß, resulting in an augmentation of T(h)17-dominant pathology.METHODS:
To determine the feedback effect, if any, of IL-17 and/or IL-22 on the secretion of IL-1ß from keratinocytes, we stimulated the human keratinocyte cell line HaCaT, as well as caspase-1-deficient mice, with IL-17 or IL-22.RESULTS:
We found that treatment with IL-17 and IL-22 causes an increase in IL-1ß via the activation of NLRP3 by a process that involves the generation of reactive oxygen species. Moreover, skin inflammation induced by IL-17 and IL-22 was lower in caspase-1 knockout (KO) mice relative to that induced by IL-1ß treatment. Additionally, skin inflammation induced by the drug imiquimod was lower in caspase-1 KO mice than in wild-type mice.CONCLUSION:
These results indicate that cytokines from T(h)17 cells may potentiate IL-1ß-mediated skin inflammation and result in phenotypic alterations of keratinocytes via a feedback mechanism.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pele
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Transdução de Sinais
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Queratinócitos
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Interleucinas
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Interleucina-17
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Interleucina-1beta
Limite:
Animals
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Humans
Idioma:
En
Revista:
Int Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2012
Tipo de documento:
Article