IL-18 and skin inflammation.
IL-18 belongs to the IL-1 family of cytokines and has recently regained interest in the context of inflammasome activation. The inflammasome dependent caspase 1 cleaves pro-IL-18 into the active form - similar to what is known for IL-1ss. Still, the action and importance of IL-18 are not completely understood. There are several indications that it plays a pathogenetically important role in chronic inflammatory conditions of epithelial organs (such as skin, gut, kidney) and importantly also in responses against self. Here, we summarise current knowledge on the role of IL-18 in human skin inflammation with a focus on its role in Cutaneous Lupus Erythematosus (CLE). There is evidence that IL-18 plays a role in CLE upstream of TNFalpha. In CLE but not normal keratinocytes IL-18 strongly induces TNFalpha release, which then results in apoptosis. Blocking TNFalpha in vitro prevents apoptosis of keratinocytes but anti-TNFalpha therapy is not applicable in LE conditions. We will discuss potential approaches to control IL-18 in skin inflammation.
Wittmann
Miriam
M
Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK. M.Wittmann@leeds.ac.uk
Macdonald
Andrew
A
Renne
Julius
J
D020170:Caspase 1 / Q000276:immunology / Q000378:metabolism; D004848:Epithelium / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007167:Immunotherapy; D036341:Intercellular Signaling Peptides and Proteins / Q000627:therapeutic use; D020382:Interleukin-18 / Q000276:immunology / Q000378:metabolism*; D053583:Interleukin-1beta / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008178:Lupus Erythematosus, Cutaneous / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D015398:Signal Transduction; D012867:Skin / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; C118370:interleukin-18 binding protein; D020170:Caspase 1