Cryopyrin-associated periodic syndromes: background and therapeutics

It has long been known that human keratinocytes are a potent source of the proinflammatory cytokines proIL-1alpha and -1beta[1], 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].