| First Author | Cho KA | Year | 2012 |
| Journal | Int Immunol | Volume | 24 |
| Issue | 3 | Pages | 147-58 |
| PubMed ID | 22207130 | Mgi Jnum | J:182570 |
| Mgi Id | MGI:5315846 | Doi | 10.1093/intimm/dxr110 |
| Citation | Cho KA, et al. (2012) IL-17 and IL-22 enhance skin inflammation by stimulating the secretion of IL-1beta by keratinocytes via the ROS-NLRP3-caspase-1 pathway. Int Immunol 24(3):147-58 |
| abstractText | BACKGROUND: The pathogenesis of inflammatory skin disease involves the release of cytokines from keratinocytes, and one of these, IL-1beta, 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-1beta receptors and secrete cytokines such as IL-17 and IL-22 in response to IL-1beta stimulation. A mutation in the inflammasome protein NLRP3 (NACHT, LRR and PYD domains-containing protein 3) causes excess production of IL-1beta, 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-1beta 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-1beta 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-1beta 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-1beta-mediated skin inflammation and result in phenotypic alterations of keratinocytes via a feedback mechanism. |
