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IL-20: a new target for the treatment of inflammatory skin disease
1Harvard Skin Disease Research Center, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. brich@rics.bwh.harvard.edu
The discovery of dramatic pro-inflammatory effects of IL-20 on skin highlighted a novel regulatory pathway in cutaneous inflammation. Specific receptor complexes for IL-20 are induced on keratinocytes and transmit potent signals via the signal transducer and activator of transcription-3. In response to IL-20, keratinocytes proliferate and express pro-inflammatory genes including TNF-alpha, which leads to activation of NF-kappaB. Recently, two related cytokines, IL-19 and IL-24, have been shown to trigger the IL-20 receptor, and a second receptor complex has also been found to respond to IL-20 and IL-24. IL-20 signalling appears to be a prominent component of cutaneous inflammation, but the extent to which inflammatory processes rely upon it is unknown. Nonetheless, the prevalence of diseases involving pathological cutaneous inflammation makes the identification of safe and effective anti-inflammatory therapies for the skin a priority. Detailed understanding of the signal transduction pathways by which the skin responds to IL-20 and related factors may make it possible to develop new pharmaceutical agents to selectively suppress cutaneous inflammation.
The discovery of dramatic pro-inflammatory effects of IL-20 on skin highlighted a novel regulatory pathway in cutaneous inflammation. Specific receptor complexes for IL-20 are induced on keratinocytes and transmit potent signals via the signal transducer and activator of transcription-3. In response to IL-20, keratinocytes proliferate and express pro-inflammatory genes including TNF-alpha, which leads to activation of NF-kappaB. Recently, two related cytokines, IL-19 and IL-24, have been shown to trigger the IL-20 receptor, and a second receptor complex has also been found to respond to IL-20 and IL-24. IL-20 signalling appears to be a prominent component of cutaneous inflammation, but the extent to which inflammatory processes rely upon it is unknown. Nonetheless, the prevalence of diseases involving pathological cutaneous inflammation makes the identification of safe and effective anti-inflammatory therapies for the skin a priority. Detailed understanding of the signal transduction pathways by which the skin responds to IL-20 and related factors may make it possible to develop new pharmaceutical agents to selectively suppress cutaneous inflammation.
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