IL-17F regulates psoriasis-associated genes through IκBζ

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

IL-17F regulates psoriasis-associated genes through IκBζ. / Bertelsen, Trine; Ljungberg, Christine; Kjellerup, Rasmus Boye; Iversen, Lars; Johansen, Claus.

In: Experimental Dermatology, 30.08.2016.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

APA

CBE

MLA

Vancouver

Author

Bertelsen, Trine ; Ljungberg, Christine ; Kjellerup, Rasmus Boye ; Iversen, Lars ; Johansen, Claus. / IL-17F regulates psoriasis-associated genes through IκBζ. In: Experimental Dermatology. 2016.

Bibtex

@article{4277a92821b54b77b304c942ceb981fd,
title = "IL-17F regulates psoriasis-associated genes through IκBζ",
abstract = "Psoriasis is a common chronic inflammatory and immune-mediated skin disease. Antagonists of TNFα and, recently, IL-17 have proven to be highly effective in the treatment of psoriasis; however, the molecular mechanisms involved in the pathogenesis of psoriasis are poorly understood. Recently, we presented evidence that IκBζ is a key regulator in the development of psoriasis through its role in mediating IL-17A-driven effects. Like IL-17A, IL-17F is produced by a variety of immune cells, and the expression of IL-17F is increased in psoriatic skin. The purpose of this study was to characterize the role of IL-17F in the regulation of IκBζ expression and to investigate whether IL-17F regulates psoriasis-associated genes in human keratinocytes through IκBζ. Here, we demonstrate that IL-17F stimulation induces IκBζ expression at both the mRNA and the protein levels in normal human keratinocytes. Moreover, silencing IκBζ by siRNA revealed that IκBζ is a key regulator of specific IL-17F-inducible psoriasis-associated genes and proteins, including DEFB4/hBD2, S100A7, CCL20, IL-8 and CHI3L1. In addition, IL-17F-induced IκBζ expression is mediated by a mechanism involving the p38 MAPK and NF-κB signalling pathways, as shown by the clear reduction in IL-17F-mediated expression of IκBζ during chemical inhibition of these two signalling pathways. In summary, we present IκBζ as a novel key regulator of IL-17F-driven effects in psoriasis. Thus, antagonists to IκBζ could potentially provide a more targeted approach for treating psoriasis as well as for treating the other inflammatory and immune-mediated diseases for which IL-17-targeting drugs have recently been approved. This article is protected by copyright. All rights reserved.",
author = "Trine Bertelsen and Christine Ljungberg and Kjellerup, {Rasmus Boye} and Lars Iversen and Claus Johansen",
note = "This article is protected by copyright. All rights reserved.",
year = "2016",
month = aug,
day = "30",
doi = "10.1111/exd.13182",
language = "English",
journal = "Experimental Dermatology",
issn = "0906-6705",
publisher = "Wiley-Blackwell Publishing Ltd.",

}

RIS

TY - JOUR

T1 - IL-17F regulates psoriasis-associated genes through IκBζ

AU - Bertelsen, Trine

AU - Ljungberg, Christine

AU - Kjellerup, Rasmus Boye

AU - Iversen, Lars

AU - Johansen, Claus

N1 - This article is protected by copyright. All rights reserved.

PY - 2016/8/30

Y1 - 2016/8/30

N2 - Psoriasis is a common chronic inflammatory and immune-mediated skin disease. Antagonists of TNFα and, recently, IL-17 have proven to be highly effective in the treatment of psoriasis; however, the molecular mechanisms involved in the pathogenesis of psoriasis are poorly understood. Recently, we presented evidence that IκBζ is a key regulator in the development of psoriasis through its role in mediating IL-17A-driven effects. Like IL-17A, IL-17F is produced by a variety of immune cells, and the expression of IL-17F is increased in psoriatic skin. The purpose of this study was to characterize the role of IL-17F in the regulation of IκBζ expression and to investigate whether IL-17F regulates psoriasis-associated genes in human keratinocytes through IκBζ. Here, we demonstrate that IL-17F stimulation induces IκBζ expression at both the mRNA and the protein levels in normal human keratinocytes. Moreover, silencing IκBζ by siRNA revealed that IκBζ is a key regulator of specific IL-17F-inducible psoriasis-associated genes and proteins, including DEFB4/hBD2, S100A7, CCL20, IL-8 and CHI3L1. In addition, IL-17F-induced IκBζ expression is mediated by a mechanism involving the p38 MAPK and NF-κB signalling pathways, as shown by the clear reduction in IL-17F-mediated expression of IκBζ during chemical inhibition of these two signalling pathways. In summary, we present IκBζ as a novel key regulator of IL-17F-driven effects in psoriasis. Thus, antagonists to IκBζ could potentially provide a more targeted approach for treating psoriasis as well as for treating the other inflammatory and immune-mediated diseases for which IL-17-targeting drugs have recently been approved. This article is protected by copyright. All rights reserved.

AB - Psoriasis is a common chronic inflammatory and immune-mediated skin disease. Antagonists of TNFα and, recently, IL-17 have proven to be highly effective in the treatment of psoriasis; however, the molecular mechanisms involved in the pathogenesis of psoriasis are poorly understood. Recently, we presented evidence that IκBζ is a key regulator in the development of psoriasis through its role in mediating IL-17A-driven effects. Like IL-17A, IL-17F is produced by a variety of immune cells, and the expression of IL-17F is increased in psoriatic skin. The purpose of this study was to characterize the role of IL-17F in the regulation of IκBζ expression and to investigate whether IL-17F regulates psoriasis-associated genes in human keratinocytes through IκBζ. Here, we demonstrate that IL-17F stimulation induces IκBζ expression at both the mRNA and the protein levels in normal human keratinocytes. Moreover, silencing IκBζ by siRNA revealed that IκBζ is a key regulator of specific IL-17F-inducible psoriasis-associated genes and proteins, including DEFB4/hBD2, S100A7, CCL20, IL-8 and CHI3L1. In addition, IL-17F-induced IκBζ expression is mediated by a mechanism involving the p38 MAPK and NF-κB signalling pathways, as shown by the clear reduction in IL-17F-mediated expression of IκBζ during chemical inhibition of these two signalling pathways. In summary, we present IκBζ as a novel key regulator of IL-17F-driven effects in psoriasis. Thus, antagonists to IκBζ could potentially provide a more targeted approach for treating psoriasis as well as for treating the other inflammatory and immune-mediated diseases for which IL-17-targeting drugs have recently been approved. This article is protected by copyright. All rights reserved.

U2 - 10.1111/exd.13182

DO - 10.1111/exd.13182

M3 - Journal article

C2 - 27576147

JO - Experimental Dermatology

JF - Experimental Dermatology

SN - 0906-6705

ER -