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Th17 micro-milieu regulates NLRP1-dependent caspase-5 activity in skin autoinflammation.

Abstract IL-1β is a potent player in cutaneous inflammation and central for the development of a Th17 micro-milieu in autoinflammatory diseases including psoriasis. Its production is controlled at the transcriptional level and by subsequent posttranslational processing via inflammatory caspases. In this study, we detected inflammatory caspase-5 active in epidermal keratinocytes and in psoriatic skin lesions. Further, interferon-γ and interleukin-17A synergistically induced caspase-5 expression in cultured keratinocytes, which was dependent on the antimicrobial peptide psoriasin (S100A7). However, diseases-relevant triggers for caspase-5 activity and IL-1β production remain unknown. Recently, extranuclear DNA has been identified as danger-signals abundant in the psoriatic epidermis. Here, we could demonstrate that cytosolic double-stranded (ds) DNA transfected into keratinocytes triggered the activation of caspase-5 and the release of IL-1β. Further, interleukin-17A promoted caspase-5 function via facilitation of the NLRP1-inflammasome. Anti-inflammatory vitamin D interfered with the IL-1β release and suppressed caspase-5 in keratinocytes and in psoriatic skin lesions. Our data link the disease-intrinsic danger signals psoriasin (S100A7) and dsDNA for NLPR1-dependent caspase-5 activity in psoriasis providing potential therapeutic targets in Th17-mediated skin autoinflammation.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title plos one
Publication Year Start




PMID- 28422993
OWN - NLM
STAT- In-Process
DA  - 20170419
LR  - 20170419
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 4
DP  - 2017
TI  - Th17 micro-milieu regulates NLRP1-dependent caspase-5 activity in skin
      autoinflammation.
PG  - e0175153
LID - 10.1371/journal.pone.0175153 [doi]
AB  - IL-1beta is a potent player in cutaneous inflammation and central for the
      development of a Th17 micro-milieu in autoinflammatory diseases including
      psoriasis. Its production is controlled at the transcriptional level and by
      subsequent posttranslational processing via inflammatory caspases. In this study,
      we detected inflammatory caspase-5 active in epidermal keratinocytes and in
      psoriatic skin lesions. Further, interferon-gamma and interleukin-17A
      synergistically induced caspase-5 expression in cultured keratinocytes, which was
      dependent on the antimicrobial peptide psoriasin (S100A7). However,
      diseases-relevant triggers for caspase-5 activity and IL-1beta production remain 
      unknown. Recently, extranuclear DNA has been identified as danger-signals
      abundant in the psoriatic epidermis. Here, we could demonstrate that cytosolic
      double-stranded (ds) DNA transfected into keratinocytes triggered the activation 
      of caspase-5 and the release of IL-1beta. Further, interleukin-17A promoted
      caspase-5 function via facilitation of the NLRP1-inflammasome. Anti-inflammatory 
      vitamin D interfered with the IL-1beta release and suppressed caspase-5 in
      keratinocytes and in psoriatic skin lesions. Our data link the disease-intrinsic 
      danger signals psoriasin (S100A7) and dsDNA for NLPR1-dependent caspase-5
      activity in psoriasis providing potential therapeutic targets in Th17-mediated
      skin autoinflammation.
FAU - Zwicker, Stephanie
AU  - Zwicker S
AD  - Department of Dermatology and Allergology, Ludwig-Maximilian University Munich,
      Frauenlobstr. 9-11, Munich, Germany.
AD  - Department of Dental Medicine, Karolinska Institute, Alfred Nobels Alle 8,
      Huddinge, Sweden.
FAU - Hattinger, Eva
AU  - Hattinger E
AD  - Department of Dermatology and Allergology, Ludwig-Maximilian University Munich,
      Frauenlobstr. 9-11, Munich, Germany.
FAU - Bureik, Daniela
AU  - Bureik D
AD  - Department of Dermatology and Allergology, Ludwig-Maximilian University Munich,
      Frauenlobstr. 9-11, Munich, Germany.
FAU - Batycka-Baran, Aleksandra
AU  - Batycka-Baran A
AD  - Department of Dermatology and Allergology, Ludwig-Maximilian University Munich,
      Frauenlobstr. 9-11, Munich, Germany.
AD  - Department of Dermatology, Venereology and Allergy, Wroclaw Medical University,
      Chalubinskiego 1, Wroclaw, Poland.
FAU - Schmidt, Andreas
AU  - Schmidt A
AD  - Division of Clinical Pharmacology, Medizinische Klinik IV, Ludwig-Maximilian
      University Munich, Ziemssenstr. 1, Munich, Germany.
FAU - Gerber, Peter-Arne
AU  - Gerber PA
AD  - Department of Dermatology, University Hospital Dusseldorf, Moorenstrasse 5,
      Dusseldorf, Germany.
FAU - Rothenfusser, Simon
AU  - Rothenfusser S
AD  - Division of Clinical Pharmacology, Medizinische Klinik IV, Ludwig-Maximilian
      University Munich, Ziemssenstr. 1, Munich, Germany.
FAU - Gilliet, Michel
AU  - Gilliet M
AD  - Department of Dermatology, University Hospital of Lausanne, CHUV University
      Hospital, Rue du Bugnon 46, Lausanne, Switzerland.
FAU - Ruzicka, Thomas
AU  - Ruzicka T
AD  - Department of Dermatology and Allergology, Ludwig-Maximilian University Munich,
      Frauenlobstr. 9-11, Munich, Germany.
FAU - Wolf, Ronald
AU  - Wolf R
AD  - Department of Dermatology and Allergology, Ludwig-Maximilian University Munich,
      Frauenlobstr. 9-11, Munich, Germany.
AD  - Department of Dermatology and Allergology, Philipps University Marburg, Marburg, 
      Germany.
LA  - eng
PT  - Journal Article
DEP - 20170419
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
EDAT- 2017/04/20 06:00
MHDA- 2017/04/20 06:00
CRDT- 2017/04/20 06:00
PHST- 2016/06/28 [received]
PHST- 2017/03/21 [accepted]
AID - 10.1371/journal.pone.0175153 [doi]
AID - PONE-D-16-25938 [pii]
PST - epublish
SO  - PLoS One. 2017 Apr 19;12(4):e0175153. doi: 10.1371/journal.pone.0175153.
      eCollection 2017.

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