title: Inflammasome activation and IL-1β target IL-1α for secretion as opposed to surface expression.
abstract: Interleukin-1α (IL-1α) and -β both bind to the same IL-1 receptor (IL-1R) and are potent proinflammatory cytokines. Production of proinflammatory (pro)-IL-1α and pro-IL-1β is induced by Toll-like receptor (TLR)-mediated NF-κB activation. Additional stimulus involving activation of the inflammasome and caspase-1 is required for proteolytic cleavage and secretion of mature IL-1β. The regulation of IL-1α maturation and secretion, however, remains elusive. IL-1α exists as a cell surface-associated form and as a mature secreted form. Here we show that both forms of IL-1α, the surface and secreted form, are differentially regulated. Surface IL-1α requires NF-κB activation only, whereas secretion of mature IL-1α requires additional activation of the inflammasome and caspase-1. Surprisingly, secretion of IL-1α also required the presence of IL-1β, as demonstrated in IL-1β-deficient mice. We further demonstrate that IL-1β directly binds IL-1α, thus identifying IL-1β as a shuttle for another proinflammatory cytokine. These results have direct impact on selective treatment modalities of inflammatory diseases.
authors: Department of Dermatology, Zurich University Hospital, 8091 Zurich, Switzerland. antonia.fettelschoss@usz.ch
authors: Antonia
authors: A
authors: Fettelschoss
authors: Magdalena
authors: M
authors: Kistowska
authors: Salomé
authors: S
authors: LeibundGut-Landmann
authors: Hans-Dietmar
authors: HD
authors: Beer
authors: Pål
authors: P
authors: Johansen
authors: Gabriela
authors: G
authors: Senti
authors: Emmanuel
authors: E
authors: Contassot
authors: Martin F
authors: MF
authors: Bachmann
authors: Lars E
authors: LE
authors: French
authors: Annette
authors: A
authors: Oxenius
authors: Thomas M
authors: TM
authors: Kündig
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology*; D053582:Interleukin-1alpha / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology*; D051379:Mice
chemical_list: D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D020170:Caspase 1