Cargando…

PRINS Non-Coding RNA Regulates Nucleic Acid-Induced Innate Immune Responses of Human Keratinocytes

Cytosolic DNA fragments are recognized as pathogen- and danger-associated molecular patterns that induce a cascade of innate immune responses. Moreover, excessive cytosolic DNA can enhance chronic inflammation, predominantly by activating inflammasomes, and thereby contributing to the pathogenesis o...

Descripción completa

Detalles Bibliográficos
Autores principales: Danis, Judit, Göblös, Anikó, Bata-Csörgő, Zsuzsanna, Kemény, Lajos, Széll, Márta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581800/
https://www.ncbi.nlm.nih.gov/pubmed/28900430
http://dx.doi.org/10.3389/fimmu.2017.01053
_version_ 1783261095176175616
author Danis, Judit
Göblös, Anikó
Bata-Csörgő, Zsuzsanna
Kemény, Lajos
Széll, Márta
author_facet Danis, Judit
Göblös, Anikó
Bata-Csörgő, Zsuzsanna
Kemény, Lajos
Széll, Márta
author_sort Danis, Judit
collection PubMed
description Cytosolic DNA fragments are recognized as pathogen- and danger-associated molecular patterns that induce a cascade of innate immune responses. Moreover, excessive cytosolic DNA can enhance chronic inflammation, predominantly by activating inflammasomes, and thereby contributing to the pathogenesis of chronic diseases, such as psoriasis. Psoriasis associated non-protein coding RNA induced by stress (PRINS) is a long non-coding RNA, which has been shown to be associated with psoriasis susceptibility and cellular stress responses; however, the precise mechanism of its action has not been determined. Here, we provide evidence that, in addition to inflammasome activation, cytosolic DNA induces intracellular inflammatory reactions while decreasing PRINS gene expression. Furthermore, PRINS overexpression can ameliorate the inflammatory-mediator production of keratinocytes induced by cytosolic DNA. Overexpression of PRINS resulted in decreased interleukin-6 (IL-6) and chemokine (C–C motif) ligand 5 (CCL-5) expression and secretion. In silico analysis predicted direct binding sites between PRINS and the mRNAs, which was confirmed by an in vitro binding assay and on cellular level. Our results indicated that PRINS binds directly to the mRNAs of IL-6 and CCL-5 at specific binding sites and eventually destabilizes these mRNAs, leading to a decrease in their expression and secretion of the corresponding proteins. These results may indicate a restrictive role for PRINS in inflammatory processes.
format Online
Article
Text
id pubmed-5581800
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-55818002017-09-12 PRINS Non-Coding RNA Regulates Nucleic Acid-Induced Innate Immune Responses of Human Keratinocytes Danis, Judit Göblös, Anikó Bata-Csörgő, Zsuzsanna Kemény, Lajos Széll, Márta Front Immunol Immunology Cytosolic DNA fragments are recognized as pathogen- and danger-associated molecular patterns that induce a cascade of innate immune responses. Moreover, excessive cytosolic DNA can enhance chronic inflammation, predominantly by activating inflammasomes, and thereby contributing to the pathogenesis of chronic diseases, such as psoriasis. Psoriasis associated non-protein coding RNA induced by stress (PRINS) is a long non-coding RNA, which has been shown to be associated with psoriasis susceptibility and cellular stress responses; however, the precise mechanism of its action has not been determined. Here, we provide evidence that, in addition to inflammasome activation, cytosolic DNA induces intracellular inflammatory reactions while decreasing PRINS gene expression. Furthermore, PRINS overexpression can ameliorate the inflammatory-mediator production of keratinocytes induced by cytosolic DNA. Overexpression of PRINS resulted in decreased interleukin-6 (IL-6) and chemokine (C–C motif) ligand 5 (CCL-5) expression and secretion. In silico analysis predicted direct binding sites between PRINS and the mRNAs, which was confirmed by an in vitro binding assay and on cellular level. Our results indicated that PRINS binds directly to the mRNAs of IL-6 and CCL-5 at specific binding sites and eventually destabilizes these mRNAs, leading to a decrease in their expression and secretion of the corresponding proteins. These results may indicate a restrictive role for PRINS in inflammatory processes. Frontiers Media S.A. 2017-08-29 /pmc/articles/PMC5581800/ /pubmed/28900430 http://dx.doi.org/10.3389/fimmu.2017.01053 Text en Copyright © 2017 Danis, Göblös, Bata-Csörgő, Kemény and Széll. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Danis, Judit
Göblös, Anikó
Bata-Csörgő, Zsuzsanna
Kemény, Lajos
Széll, Márta
PRINS Non-Coding RNA Regulates Nucleic Acid-Induced Innate Immune Responses of Human Keratinocytes
title PRINS Non-Coding RNA Regulates Nucleic Acid-Induced Innate Immune Responses of Human Keratinocytes
title_full PRINS Non-Coding RNA Regulates Nucleic Acid-Induced Innate Immune Responses of Human Keratinocytes
title_fullStr PRINS Non-Coding RNA Regulates Nucleic Acid-Induced Innate Immune Responses of Human Keratinocytes
title_full_unstemmed PRINS Non-Coding RNA Regulates Nucleic Acid-Induced Innate Immune Responses of Human Keratinocytes
title_short PRINS Non-Coding RNA Regulates Nucleic Acid-Induced Innate Immune Responses of Human Keratinocytes
title_sort prins non-coding rna regulates nucleic acid-induced innate immune responses of human keratinocytes
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581800/
https://www.ncbi.nlm.nih.gov/pubmed/28900430
http://dx.doi.org/10.3389/fimmu.2017.01053
work_keys_str_mv AT danisjudit prinsnoncodingrnaregulatesnucleicacidinducedinnateimmuneresponsesofhumankeratinocytes
AT goblosaniko prinsnoncodingrnaregulatesnucleicacidinducedinnateimmuneresponsesofhumankeratinocytes
AT batacsorgozsuzsanna prinsnoncodingrnaregulatesnucleicacidinducedinnateimmuneresponsesofhumankeratinocytes
AT kemenylajos prinsnoncodingrnaregulatesnucleicacidinducedinnateimmuneresponsesofhumankeratinocytes
AT szellmarta prinsnoncodingrnaregulatesnucleicacidinducedinnateimmuneresponsesofhumankeratinocytes