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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01053/full |
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| author | Judit Danis Judit Danis Anikó Göblös Anikó Göblös Zsuzsanna Bata-Csörgő Zsuzsanna Bata-Csörgő Lajos Kemény Lajos Kemény Márta Széll Márta Széll |
| author_facet | Judit Danis Judit Danis Anikó Göblös Anikó Göblös Zsuzsanna Bata-Csörgő Zsuzsanna Bata-Csörgő Lajos Kemény Lajos Kemény Márta Széll Márta Széll |
| author_sort | Judit Danis |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T19:54:09Z |
| format | Article |
| id | doaj.art-e74fc9a234e34c09b32d33d5ce128e13 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T19:54:09Z |
| publishDate | 2017-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e74fc9a234e34c09b32d33d5ce128e132022-12-22T02:32:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-08-01810.3389/fimmu.2017.01053289506PRINS Non-Coding RNA Regulates Nucleic Acid-Induced Innate Immune Responses of Human KeratinocytesJudit Danis0Judit Danis1Anikó Göblös2Anikó Göblös3Zsuzsanna Bata-Csörgő4Zsuzsanna Bata-Csörgő5Lajos Kemény6Lajos Kemény7Márta Széll8Márta Széll9Department of Dermatology and Allergology, University of Szeged, Szeged, HungaryMTA-SZTE Dermatological Research Group, Szeged, HungaryDepartment of Dermatology and Allergology, University of Szeged, Szeged, HungaryMTA-SZTE Dermatological Research Group, Szeged, HungaryDepartment of Dermatology and Allergology, University of Szeged, Szeged, HungaryMTA-SZTE Dermatological Research Group, Szeged, HungaryDepartment of Dermatology and Allergology, University of Szeged, Szeged, HungaryMTA-SZTE Dermatological Research Group, Szeged, HungaryMTA-SZTE Dermatological Research Group, Szeged, HungaryDepartment of Medical Genetics, University of Szeged, Szeged, HungaryCytosolic 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.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01053/fullPRINSlong non-coding RNAinterleukin-6CCL-5keratinocytepoly(dA:dT) |
| spellingShingle | Judit Danis Judit Danis Anikó Göblös Anikó Göblös Zsuzsanna Bata-Csörgő Zsuzsanna Bata-Csörgő Lajos Kemény Lajos Kemény Márta Széll Márta Széll PRINS Non-Coding RNA Regulates Nucleic Acid-Induced Innate Immune Responses of Human Keratinocytes Frontiers in Immunology PRINS long non-coding RNA interleukin-6 CCL-5 keratinocyte poly(dA:dT) |
| 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 | PRINS long non-coding RNA interleukin-6 CCL-5 keratinocyte poly(dA:dT) |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01053/full |
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