The inflammasome mediates UVB-induced activation and secretion of interleukin-1beta by keratinocytes.
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].
Feldmeyer
Laurence
L
Institute of Cell Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
Keller
Martin
M
Niklaus
Gisela
G
Hohl
Daniel
D
Werner
Sabine
S
Beer
Hans-Dietmar
HD
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D003872:Dermatitis / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism* / Q000528:radiation effects; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D014466:Ultraviolet Rays
D016207:Cytokines; D018836:Inflammation Mediators; D007375:Interleukin-1; D053583:Interleukin-1beta; D046912:Multiprotein Complexes; D011498:Protein Precursors; C043830:interleukin 1 precursor; D020170:Caspase 1; D002118:Calcium