The inflammasome mediates UVB-induced activation and secretion of interleukin-1beta by keratinocytes |
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Authors: | Feldmeyer Laurence Keller Martin Niklaus Gisela Hohl Daniel Werner Sabine Beer Hans-Dietmar |
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Institution: | Institute of Cell Biology, Department of Biology, ETH Zurich, Zurich, Switzerland. |
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Abstract: | It has long been known that human keratinocytes are a potent source of the proinflammatory cytokines proIL-1alpha and -1beta1], which are activated and released in response to UV irradiation 2]. However, the intracellular pathways, which regulate maturation and secretion of IL-1 in keratinocytes, are unknown. Here we show that the UVB-mediated enhancement of cytoplasmic Ca(2+) is required for activation of the IL-1beta-converting enzyme caspase-1 by the inflammasome, a multiprotein innate immune complex 3, 4]. Caspase-1 in turn activates proIL-1beta, and keratinocytes secrete the cytokine as well as inflammasome components. These results demonstrate the presence of a proIL-1beta-processing inflammasome in nonprofessional immune cells and the necessity of inflammasome components for the UVB-induced secretion of IL-1beta. This supports the concept that keratinocytes are important immuno-competent cells under physiological and pathological conditions 5]. |
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