Keratinocytes express functional CARD18, a negative regulator of inflammasome activation, and its altered expression in psoriasis may contribute to disease pathogenesis

Anikó Göblös, Judit Danis, Krisztina Vas, Z. Bata-Csörgő, L. Kemény, M. Széll

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Caspase recruitment domain family member 18 (CARD18, Iceberg) is known as a negative regulatory molecule that inhibits inflammatory events by terminating inflammasome activation due to a direct interaction with pro-caspase-1.During the investigation of molecular mechanisms in keratinocytes that contribute to the pathogenesis of psoriasis, we found that CARD18 expression differs in healthy and psoriatic skin; moreover, CARD18 demonstrated altered response under inflammatory conditions in healthy and psoriatic skin. In healthy skin, low basal CARD18 expression was detected, which showed significant elevation in response to inflammatory stimuli (lymphokine treatment or mechanical injury). In contrast, higher basal expression was observed in psoriatic non-involved skin, but no further induction could be detected. We demonstrated that keratinocytes express CARD18 both at mRNA and protein levels and the expression increased in parallel with differentiation. The investigation of cellular inflammatory processes revealed that psoriasis-associated danger signals triggered the expression of inflammasome components (AIM2, Caspase-1) and CARD18 as well as IL-1β production of keratinocytes. Furthermore, gene-specific silencing of CARD18 in cells treated with cytosolic DNA (poly(dA:dT)) resulted in increased IL-1β secretion, suggesting a negative regulatory role for CARD18 in keratinocyte inflammatory signaling. The differential regulation of CARD18 in healthy and psoriatic uninvolved epidermis may contribute to the susceptibility of psoriasis. Furthermore, our in vitro results indicate that CARD18 may contribute to the fine tuning of keratinocyte innate immune processes.

Original languageEnglish
Pages (from-to)10-18
Number of pages9
JournalMolecular Immunology
Volume73
DOIs
Publication statusPublished - May 1 2016

Fingerprint

Inflammasomes
Keratinocytes
Psoriasis
Caspase 1
Skin
Interleukin-1
Poly dA-dT
Ice Cover
Lymphokines
Gene Silencing
Epidermis
Messenger RNA
DNA
Wounds and Injuries
Proteins

Keywords

  • AIM2
  • CARD18
  • Caspase-1
  • IL-1β
  • Inflammation
  • Psoriasis

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

Cite this

@article{c8e0c1ca21e34501b1d520db02bf9dfe,
title = "Keratinocytes express functional CARD18, a negative regulator of inflammasome activation, and its altered expression in psoriasis may contribute to disease pathogenesis",
abstract = "Caspase recruitment domain family member 18 (CARD18, Iceberg) is known as a negative regulatory molecule that inhibits inflammatory events by terminating inflammasome activation due to a direct interaction with pro-caspase-1.During the investigation of molecular mechanisms in keratinocytes that contribute to the pathogenesis of psoriasis, we found that CARD18 expression differs in healthy and psoriatic skin; moreover, CARD18 demonstrated altered response under inflammatory conditions in healthy and psoriatic skin. In healthy skin, low basal CARD18 expression was detected, which showed significant elevation in response to inflammatory stimuli (lymphokine treatment or mechanical injury). In contrast, higher basal expression was observed in psoriatic non-involved skin, but no further induction could be detected. We demonstrated that keratinocytes express CARD18 both at mRNA and protein levels and the expression increased in parallel with differentiation. The investigation of cellular inflammatory processes revealed that psoriasis-associated danger signals triggered the expression of inflammasome components (AIM2, Caspase-1) and CARD18 as well as IL-1β production of keratinocytes. Furthermore, gene-specific silencing of CARD18 in cells treated with cytosolic DNA (poly(dA:dT)) resulted in increased IL-1β secretion, suggesting a negative regulatory role for CARD18 in keratinocyte inflammatory signaling. The differential regulation of CARD18 in healthy and psoriatic uninvolved epidermis may contribute to the susceptibility of psoriasis. Furthermore, our in vitro results indicate that CARD18 may contribute to the fine tuning of keratinocyte innate immune processes.",
keywords = "AIM2, CARD18, Caspase-1, IL-1β, Inflammation, Psoriasis",
author = "Anik{\'o} G{\"o}bl{\"o}s and Judit Danis and Krisztina Vas and Z. Bata-Cs{\"o}rgő and L. Kem{\'e}ny and M. Sz{\'e}ll",
year = "2016",
month = "5",
day = "1",
doi = "10.1016/j.molimm.2016.03.009",
language = "English",
volume = "73",
pages = "10--18",
journal = "Molecular Immunology",
issn = "0161-5890",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Keratinocytes express functional CARD18, a negative regulator of inflammasome activation, and its altered expression in psoriasis may contribute to disease pathogenesis

AU - Göblös, Anikó

AU - Danis, Judit

AU - Vas, Krisztina

AU - Bata-Csörgő, Z.

AU - Kemény, L.

AU - Széll, M.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Caspase recruitment domain family member 18 (CARD18, Iceberg) is known as a negative regulatory molecule that inhibits inflammatory events by terminating inflammasome activation due to a direct interaction with pro-caspase-1.During the investigation of molecular mechanisms in keratinocytes that contribute to the pathogenesis of psoriasis, we found that CARD18 expression differs in healthy and psoriatic skin; moreover, CARD18 demonstrated altered response under inflammatory conditions in healthy and psoriatic skin. In healthy skin, low basal CARD18 expression was detected, which showed significant elevation in response to inflammatory stimuli (lymphokine treatment or mechanical injury). In contrast, higher basal expression was observed in psoriatic non-involved skin, but no further induction could be detected. We demonstrated that keratinocytes express CARD18 both at mRNA and protein levels and the expression increased in parallel with differentiation. The investigation of cellular inflammatory processes revealed that psoriasis-associated danger signals triggered the expression of inflammasome components (AIM2, Caspase-1) and CARD18 as well as IL-1β production of keratinocytes. Furthermore, gene-specific silencing of CARD18 in cells treated with cytosolic DNA (poly(dA:dT)) resulted in increased IL-1β secretion, suggesting a negative regulatory role for CARD18 in keratinocyte inflammatory signaling. The differential regulation of CARD18 in healthy and psoriatic uninvolved epidermis may contribute to the susceptibility of psoriasis. Furthermore, our in vitro results indicate that CARD18 may contribute to the fine tuning of keratinocyte innate immune processes.

AB - Caspase recruitment domain family member 18 (CARD18, Iceberg) is known as a negative regulatory molecule that inhibits inflammatory events by terminating inflammasome activation due to a direct interaction with pro-caspase-1.During the investigation of molecular mechanisms in keratinocytes that contribute to the pathogenesis of psoriasis, we found that CARD18 expression differs in healthy and psoriatic skin; moreover, CARD18 demonstrated altered response under inflammatory conditions in healthy and psoriatic skin. In healthy skin, low basal CARD18 expression was detected, which showed significant elevation in response to inflammatory stimuli (lymphokine treatment or mechanical injury). In contrast, higher basal expression was observed in psoriatic non-involved skin, but no further induction could be detected. We demonstrated that keratinocytes express CARD18 both at mRNA and protein levels and the expression increased in parallel with differentiation. The investigation of cellular inflammatory processes revealed that psoriasis-associated danger signals triggered the expression of inflammasome components (AIM2, Caspase-1) and CARD18 as well as IL-1β production of keratinocytes. Furthermore, gene-specific silencing of CARD18 in cells treated with cytosolic DNA (poly(dA:dT)) resulted in increased IL-1β secretion, suggesting a negative regulatory role for CARD18 in keratinocyte inflammatory signaling. The differential regulation of CARD18 in healthy and psoriatic uninvolved epidermis may contribute to the susceptibility of psoriasis. Furthermore, our in vitro results indicate that CARD18 may contribute to the fine tuning of keratinocyte innate immune processes.

KW - AIM2

KW - CARD18

KW - Caspase-1

KW - IL-1β

KW - Inflammation

KW - Psoriasis

UR - http://www.scopus.com/inward/record.url?scp=84961657984&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961657984&partnerID=8YFLogxK

U2 - 10.1016/j.molimm.2016.03.009

DO - 10.1016/j.molimm.2016.03.009

M3 - Article

C2 - 27023378

AN - SCOPUS:84961657984

VL - 73

SP - 10

EP - 18

JO - Molecular Immunology

JF - Molecular Immunology

SN - 0161-5890

ER -