Cargando…

Expression of inflammasome proteins and inflammasome activation occurs in human, but not in murine keratinocytes

Inflammasomes are multimeric protein complexes that assemble upon sensing of a variety of stress factors. Their formation results in caspase-1-mediated activation and secretion of the pro-inflammatory cytokines pro-interleukin(IL)-1β and -18, which induce an inflammatory response. Inflammation is su...

Descripción completa

Detalles Bibliográficos
Autores principales: Sand, Jennifer, Haertel, Eric, Biedermann, Thomas, Contassot, Emmanuel, Reichmann, Ernst, French, Lars E., Werner, Sabine, Beer, Hans-Dietmar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833864/
https://www.ncbi.nlm.nih.gov/pubmed/29348630
http://dx.doi.org/10.1038/s41419-017-0009-4
_version_ 1783303555032023040
author Sand, Jennifer
Haertel, Eric
Biedermann, Thomas
Contassot, Emmanuel
Reichmann, Ernst
French, Lars E.
Werner, Sabine
Beer, Hans-Dietmar
author_facet Sand, Jennifer
Haertel, Eric
Biedermann, Thomas
Contassot, Emmanuel
Reichmann, Ernst
French, Lars E.
Werner, Sabine
Beer, Hans-Dietmar
author_sort Sand, Jennifer
collection PubMed
description Inflammasomes are multimeric protein complexes that assemble upon sensing of a variety of stress factors. Their formation results in caspase-1-mediated activation and secretion of the pro-inflammatory cytokines pro-interleukin(IL)-1β and -18, which induce an inflammatory response. Inflammation is supported by a lytic form of cell death, termed pyroptosis. Innate immune cells, such as macrophages or dendritic cells, express and activate inflammasomes. However, it has also been demonstrated that human primary keratinocytes activate different types of inflammasomes in vitro, for example, upon UVB irradiation or viral infection. Keratinocytes are the main cell type of the epidermis, the outermost layer of the body, and form a protective barrier consisting of a stratified multi-layered epithelium. In human, gain-of-function mutations of the NLRP1 gene cause syndromes mediated by inflammasome activation in keratinocytes that are characterised by skin inflammation and skin cancer susceptibility. Here we demonstrate that murine keratinocytes do not activate inflammasomes in response to stimuli, which induce IL-1β and -18 secretion by human keratinocytes. Whereas murine keratinocytes produced caspase-1 and proIL-18, expression of the inflammasome proteins Nlrp1, Nlrp3, Aim2, Asc, and proIL-1β was, compared to human keratinocytes or murine dendritic cells, very low or even undetectable. Priming of murine keratinocytes with cytokines commonly used for induction of proIL-1β and inflammasome protein expression did not rescue inflammasome activation. Nevertheless, UVB-induced inflammation and neutrophil recruitment in murine skin was dependent on IL-1β and caspase-1. However, also under these conditions, we did not detect expression of proIL-1β by keratinocytes in murine skin, but by immune cells. These results demonstrate a higher immunological competence of human compared to murine keratinocytes, which is reflected by stress-induced IL-1β secretion that is mediated by inflammasomes. Therefore, keratinocytes in human skin can exert immune functions, which are carried out by professional immune cells in murine skin.
format Online
Article
Text
id pubmed-5833864
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-58338642018-03-06 Expression of inflammasome proteins and inflammasome activation occurs in human, but not in murine keratinocytes Sand, Jennifer Haertel, Eric Biedermann, Thomas Contassot, Emmanuel Reichmann, Ernst French, Lars E. Werner, Sabine Beer, Hans-Dietmar Cell Death Dis Article Inflammasomes are multimeric protein complexes that assemble upon sensing of a variety of stress factors. Their formation results in caspase-1-mediated activation and secretion of the pro-inflammatory cytokines pro-interleukin(IL)-1β and -18, which induce an inflammatory response. Inflammation is supported by a lytic form of cell death, termed pyroptosis. Innate immune cells, such as macrophages or dendritic cells, express and activate inflammasomes. However, it has also been demonstrated that human primary keratinocytes activate different types of inflammasomes in vitro, for example, upon UVB irradiation or viral infection. Keratinocytes are the main cell type of the epidermis, the outermost layer of the body, and form a protective barrier consisting of a stratified multi-layered epithelium. In human, gain-of-function mutations of the NLRP1 gene cause syndromes mediated by inflammasome activation in keratinocytes that are characterised by skin inflammation and skin cancer susceptibility. Here we demonstrate that murine keratinocytes do not activate inflammasomes in response to stimuli, which induce IL-1β and -18 secretion by human keratinocytes. Whereas murine keratinocytes produced caspase-1 and proIL-18, expression of the inflammasome proteins Nlrp1, Nlrp3, Aim2, Asc, and proIL-1β was, compared to human keratinocytes or murine dendritic cells, very low or even undetectable. Priming of murine keratinocytes with cytokines commonly used for induction of proIL-1β and inflammasome protein expression did not rescue inflammasome activation. Nevertheless, UVB-induced inflammation and neutrophil recruitment in murine skin was dependent on IL-1β and caspase-1. However, also under these conditions, we did not detect expression of proIL-1β by keratinocytes in murine skin, but by immune cells. These results demonstrate a higher immunological competence of human compared to murine keratinocytes, which is reflected by stress-induced IL-1β secretion that is mediated by inflammasomes. Therefore, keratinocytes in human skin can exert immune functions, which are carried out by professional immune cells in murine skin. Nature Publishing Group UK 2018-01-18 /pmc/articles/PMC5833864/ /pubmed/29348630 http://dx.doi.org/10.1038/s41419-017-0009-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Sand, Jennifer
Haertel, Eric
Biedermann, Thomas
Contassot, Emmanuel
Reichmann, Ernst
French, Lars E.
Werner, Sabine
Beer, Hans-Dietmar
Expression of inflammasome proteins and inflammasome activation occurs in human, but not in murine keratinocytes
title Expression of inflammasome proteins and inflammasome activation occurs in human, but not in murine keratinocytes
title_full Expression of inflammasome proteins and inflammasome activation occurs in human, but not in murine keratinocytes
title_fullStr Expression of inflammasome proteins and inflammasome activation occurs in human, but not in murine keratinocytes
title_full_unstemmed Expression of inflammasome proteins and inflammasome activation occurs in human, but not in murine keratinocytes
title_short Expression of inflammasome proteins and inflammasome activation occurs in human, but not in murine keratinocytes
title_sort expression of inflammasome proteins and inflammasome activation occurs in human, but not in murine keratinocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833864/
https://www.ncbi.nlm.nih.gov/pubmed/29348630
http://dx.doi.org/10.1038/s41419-017-0009-4
work_keys_str_mv AT sandjennifer expressionofinflammasomeproteinsandinflammasomeactivationoccursinhumanbutnotinmurinekeratinocytes
AT haerteleric expressionofinflammasomeproteinsandinflammasomeactivationoccursinhumanbutnotinmurinekeratinocytes
AT biedermannthomas expressionofinflammasomeproteinsandinflammasomeactivationoccursinhumanbutnotinmurinekeratinocytes
AT contassotemmanuel expressionofinflammasomeproteinsandinflammasomeactivationoccursinhumanbutnotinmurinekeratinocytes
AT reichmannernst expressionofinflammasomeproteinsandinflammasomeactivationoccursinhumanbutnotinmurinekeratinocytes
AT frenchlarse expressionofinflammasomeproteinsandinflammasomeactivationoccursinhumanbutnotinmurinekeratinocytes
AT wernersabine expressionofinflammasomeproteinsandinflammasomeactivationoccursinhumanbutnotinmurinekeratinocytes
AT beerhansdietmar expressionofinflammasomeproteinsandinflammasomeactivationoccursinhumanbutnotinmurinekeratinocytes