Cargando…
Interleukin-38 interacts with destrin/actin-depolymerizing factor in human keratinocytes
Interleukin (IL)-38 is a member of the IL-1 family of cytokines, which was proposed to exert anti-inflammatory effects. IL-38 is constitutively expressed in the skin, where keratinocytes are the main producing cells. Little information is currently available concerning IL-38 biology. Here, we invest...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879167/ https://www.ncbi.nlm.nih.gov/pubmed/31770407 http://dx.doi.org/10.1371/journal.pone.0225782 |
_version_ | 1783473569249886208 |
---|---|
author | Talabot-Ayer, Dominique Mermoud, Loïc Borowczyk, Julia Drukala, Justyna Wolnicki, Michal Modarressi, Ali Boehncke, Wolf-Henning Brembilla, Nicolo Palmer, Gaby |
author_facet | Talabot-Ayer, Dominique Mermoud, Loïc Borowczyk, Julia Drukala, Justyna Wolnicki, Michal Modarressi, Ali Boehncke, Wolf-Henning Brembilla, Nicolo Palmer, Gaby |
author_sort | Talabot-Ayer, Dominique |
collection | PubMed |
description | Interleukin (IL)-38 is a member of the IL-1 family of cytokines, which was proposed to exert anti-inflammatory effects. IL-38 is constitutively expressed in the skin, where keratinocytes are the main producing cells. Little information is currently available concerning IL-38 biology. Here, we investigated the subcellular localization and interaction partners of the IL-38 protein in human keratinocytes. IL-38 expression was reduced in primary keratinocytes grown in monolayer (2D) cultures. We thus used IL-38 overexpressing immortalized normal human keratinocytes (NHK/38) to study this cytokine in cell monolayers. In parallel, differentiation of primary human keratinocytes in an in vitro reconstructed human epidermis (RHE) 3D model allowed us to restore endogenous IL-38 expression. In NHK/38 cells and in RHE, IL-38 was mainly cell-associated, rather than released into culture supernatants. Intracellular IL-38 was preferentially, although not exclusively, cytoplasmic. Similarly, in normal human skin sections, IL-38 was predominantly cytoplasmic in the epidermis and essentially excluded from keratinocyte nuclei. A yeast two-hybrid screen identified destrin/actin-depolymerizing factor (DSTN) as a potential IL-38-interacting molecule. Co-immunoprecipitation and proximity ligation assay confirmed this interaction. We further observed partial co-localization of IL-38 and DSTN in NHK/38 cells. Endogenous IL-38 and DSTN were also co-expressed in all epidermal layers in RHE and in normal human skin. Finally, IL-38 partially co-localized with F-actin in NHK/38 cells, in particular along the cortical actin network and in filopodia. In conclusion, IL-38 is found predominantly in the cytoplasm of human keratinocytes, where it interacts with DSTN. The functional relevance of this interaction remains to be investigated. |
format | Online Article Text |
id | pubmed-6879167 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-68791672019-12-08 Interleukin-38 interacts with destrin/actin-depolymerizing factor in human keratinocytes Talabot-Ayer, Dominique Mermoud, Loïc Borowczyk, Julia Drukala, Justyna Wolnicki, Michal Modarressi, Ali Boehncke, Wolf-Henning Brembilla, Nicolo Palmer, Gaby PLoS One Research Article Interleukin (IL)-38 is a member of the IL-1 family of cytokines, which was proposed to exert anti-inflammatory effects. IL-38 is constitutively expressed in the skin, where keratinocytes are the main producing cells. Little information is currently available concerning IL-38 biology. Here, we investigated the subcellular localization and interaction partners of the IL-38 protein in human keratinocytes. IL-38 expression was reduced in primary keratinocytes grown in monolayer (2D) cultures. We thus used IL-38 overexpressing immortalized normal human keratinocytes (NHK/38) to study this cytokine in cell monolayers. In parallel, differentiation of primary human keratinocytes in an in vitro reconstructed human epidermis (RHE) 3D model allowed us to restore endogenous IL-38 expression. In NHK/38 cells and in RHE, IL-38 was mainly cell-associated, rather than released into culture supernatants. Intracellular IL-38 was preferentially, although not exclusively, cytoplasmic. Similarly, in normal human skin sections, IL-38 was predominantly cytoplasmic in the epidermis and essentially excluded from keratinocyte nuclei. A yeast two-hybrid screen identified destrin/actin-depolymerizing factor (DSTN) as a potential IL-38-interacting molecule. Co-immunoprecipitation and proximity ligation assay confirmed this interaction. We further observed partial co-localization of IL-38 and DSTN in NHK/38 cells. Endogenous IL-38 and DSTN were also co-expressed in all epidermal layers in RHE and in normal human skin. Finally, IL-38 partially co-localized with F-actin in NHK/38 cells, in particular along the cortical actin network and in filopodia. In conclusion, IL-38 is found predominantly in the cytoplasm of human keratinocytes, where it interacts with DSTN. The functional relevance of this interaction remains to be investigated. Public Library of Science 2019-11-26 /pmc/articles/PMC6879167/ /pubmed/31770407 http://dx.doi.org/10.1371/journal.pone.0225782 Text en © 2019 Talabot-Ayer et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Talabot-Ayer, Dominique Mermoud, Loïc Borowczyk, Julia Drukala, Justyna Wolnicki, Michal Modarressi, Ali Boehncke, Wolf-Henning Brembilla, Nicolo Palmer, Gaby Interleukin-38 interacts with destrin/actin-depolymerizing factor in human keratinocytes |
title | Interleukin-38 interacts with destrin/actin-depolymerizing factor in human keratinocytes |
title_full | Interleukin-38 interacts with destrin/actin-depolymerizing factor in human keratinocytes |
title_fullStr | Interleukin-38 interacts with destrin/actin-depolymerizing factor in human keratinocytes |
title_full_unstemmed | Interleukin-38 interacts with destrin/actin-depolymerizing factor in human keratinocytes |
title_short | Interleukin-38 interacts with destrin/actin-depolymerizing factor in human keratinocytes |
title_sort | interleukin-38 interacts with destrin/actin-depolymerizing factor in human keratinocytes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879167/ https://www.ncbi.nlm.nih.gov/pubmed/31770407 http://dx.doi.org/10.1371/journal.pone.0225782 |
work_keys_str_mv | AT talabotayerdominique interleukin38interactswithdestrinactindepolymerizingfactorinhumankeratinocytes AT mermoudloic interleukin38interactswithdestrinactindepolymerizingfactorinhumankeratinocytes AT borowczykjulia interleukin38interactswithdestrinactindepolymerizingfactorinhumankeratinocytes AT drukalajustyna interleukin38interactswithdestrinactindepolymerizingfactorinhumankeratinocytes AT wolnickimichal interleukin38interactswithdestrinactindepolymerizingfactorinhumankeratinocytes AT modarressiali interleukin38interactswithdestrinactindepolymerizingfactorinhumankeratinocytes AT boehnckewolfhenning interleukin38interactswithdestrinactindepolymerizingfactorinhumankeratinocytes AT brembillanicolo interleukin38interactswithdestrinactindepolymerizingfactorinhumankeratinocytes AT palmergaby interleukin38interactswithdestrinactindepolymerizingfactorinhumankeratinocytes |