The Inflammasome Mediates UVB-Induced Activation and Secretion of Interleukin-1β by Keratinocytes

Abstract

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].

A novel Nrf2-miR-29-desmocollin-2 axis regulates desmosome function in keratinocytes

“…HaCaT cells and primary human keratinocytes were transfected with miR-29 MirVana mimics (Life Technologies, Carlsbad, CA) using Interferin transfection reagent (PolyPlus Transfection, Illkirch, France) according to the manufacturer's instructions. Primary keratinocytes were isolated from newborn and adult mice using an overnight incubation with cold solution of dispase in PBS 50 . Primary human foreskin keratinocytes were obtained from healthy donors (obtained anonymously from the Department of Dermatology, University Hospital Zurich, in the context of the Biobank project, approved by the local and cantonal Research Ethics Committees) and cultured in keratinocytedefined medium (K-SFM) with supplements (Life Technologies) 50 .…”

“…Primary keratinocytes were isolated from newborn and adult mice using an overnight incubation with cold solution of dispase in PBS 50 . Primary human foreskin keratinocytes were obtained from healthy donors (obtained anonymously from the Department of Dermatology, University Hospital Zurich, in the context of the Biobank project, approved by the local and cantonal Research Ethics Committees) and cultured in keratinocytedefined medium (K-SFM) with supplements (Life Technologies) 50 . A DSC2-YFP plasmid (kindly provided by Dr Rudolf Leube, RWTH Aachen) was used for transfection of primary human keratinocytes using Lipofectamine 2,000 (Life Technologies).…”

Requirement of MyD88 signaling in keratinocytes for Langerhans cell migration and initiation of atopic dermatitis‐like symptoms in mice

“…In addition, keratinocytes can secrete proinflammatory cytokines and chemokines and alarmins, such as and thymic stromal lymphopoietin (TSLP) [18], which regulate the influx of inflammatory cells in infection and AD [19]. In addition, the inflammatory response in keratinocytes is directly triggered by Toll-like receptor (TLR) stimulation [20,21] or by environmental noxae such as UVB irradiation [20,22,23].…”

“…In addition, keratinocytes can secrete proinflammatory cytokines and chemokines and alarmins, such as and thymic stromal lymphopoietin (TSLP) [18], which regulate the influx of inflammatory cells in infection and AD [19]. In addition, the inflammatory response in keratinocytes is directly triggered by Toll-like receptor (TLR) stimulation [20,21] or by environmental noxae such as UVB irradiation [20,22,23].MyD88 is a central signal adaptor controlling the activation of most TLRs except TLR3 and is also involved in the signal transduction of cytokines of the IL-1 family [24,25]. Global MyD88 deficiency not only leads to reduced host defense in skin infections [26,27] Here, we analyze the contribution of MyD88 to the pathogenesis of AD-like dermatitis and further delineate the importance of MyD88-induced signaling in keratinocytes for development of AD-like dermatitis.…”

Novel insights into the role of immune cells in skin and inducible skin-associated lymphoid tissue (iSALT)

“…Activation of the in ammasome complex leads to subsequent activation of proin ammatory cytokines such as IL-1β and IL-18 [13]. Although it remains unclari ed which DAMPs are sensed by KCs, KCs are reported to express NLR and thus considered to sense these DAMPs [4,15]. In addition to being a sensor, KCs can also be a source of DAMPs, such as ATP [16], HMGB1 [17], IL-1, and IL-33 during in ammation [18,19].…”