Differential Inflammatory-Response Kinetics of Human Keratinocytes upon Cytosolic RNA- and DNA-Fragment Induction
Keratinocytes are non-professional immune cells contributing actively to innate immune responses partially by reacting to a wide range of molecular patterns by activating pattern recognition receptors. Cytosolic nucleotide fragments as pathogen- or self-derived trigger factors are activating inflamm...
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| Format: | Article |
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MDPI AG
2018-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | http://www.mdpi.com/1422-0067/19/3/774 |
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| author | Judit Danis Luca Janovák Barbara Gubán Anikó Göblös Kornélia Szabó Lajos Kemény Zsuzsanna Bata-Csörgő Márta Széll |
| author_facet | Judit Danis Luca Janovák Barbara Gubán Anikó Göblös Kornélia Szabó Lajos Kemény Zsuzsanna Bata-Csörgő Márta Széll |
| author_sort | Judit Danis |
| collection | DOAJ |
| description | Keratinocytes are non-professional immune cells contributing actively to innate immune responses partially by reacting to a wide range of molecular patterns by activating pattern recognition receptors. Cytosolic nucleotide fragments as pathogen- or self-derived trigger factors are activating inflammasomes and inducing anti-viral signal transduction pathways as well as inducing expression of inflammatory cytokines. We aimed to compare the induced inflammatory reactions in three keratinocyte cell types—normal human epidermal keratinocytes, the HaCaT cell line and the HPV-KER cell line—upon exposure to the synthetic RNA and DNA analogues poly(I:C) and poly(dA:dT) to reveal the underlying signaling events. Both agents induced the expression of interleukin-6 and tumor necrosis factor α in all cell types; however, notable kinetic and expression level differences were found. Western blot analysis revealed rapid activation of the nuclear factor κB (NF-κB), mitogen activated protein kinase and signal transducers of activator of transcription (STAT) signal transduction pathways in keratinocytes upon poly(I:C) treatment, while poly(dA:dT) induced slower activation. Inhibition of NF-κB, p38, STAT-1 and STAT-3 signaling resulted in decreased cytokine expression, whereas inhibition of mitogen-activated protein kinase kinase 1/2 (MEK1/2) signaling showed a negative feedback role in both poly(I:C)- and poly(dA:dT)-induced cytokine expression. Based on our in vitro results nucleotide fragments are able to induce inflammatory reactions in keratinocytes, but with different rate and kinetics of cytokine expression, explained by faster activation of signaling routes by poly(I:C) than poly(dA:dT). |
| first_indexed | 2024-04-13T18:32:03Z |
| format | Article |
| id | doaj.art-26d08170007a419ab7d494845b0f1cd1 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-13T18:32:03Z |
| publishDate | 2018-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-26d08170007a419ab7d494845b0f1cd12022-12-22T02:35:02ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-03-0119377410.3390/ijms19030774ijms19030774Differential Inflammatory-Response Kinetics of Human Keratinocytes upon Cytosolic RNA- and DNA-Fragment InductionJudit Danis0Luca Janovák1Barbara Gubán2Anikó Göblös3Kornélia Szabó4Lajos Kemény5Zsuzsanna Bata-Csörgő6Márta Széll7Department of Dermatology and Allergology, University of Szeged, 6720 Szeged, HungaryDepartment of Dermatology and Allergology, University of Szeged, 6720 Szeged, HungaryDepartment of Dermatology and Allergology, University of Szeged, 6720 Szeged, HungaryDepartment of Dermatology and Allergology, University of Szeged, 6720 Szeged, HungaryMTA-SZTE Dermatological Research Group, 6720 Szeged, HungaryDepartment of Dermatology and Allergology, University of Szeged, 6720 Szeged, HungaryDepartment of Dermatology and Allergology, University of Szeged, 6720 Szeged, HungaryMTA-SZTE Dermatological Research Group, 6720 Szeged, HungaryKeratinocytes are non-professional immune cells contributing actively to innate immune responses partially by reacting to a wide range of molecular patterns by activating pattern recognition receptors. Cytosolic nucleotide fragments as pathogen- or self-derived trigger factors are activating inflammasomes and inducing anti-viral signal transduction pathways as well as inducing expression of inflammatory cytokines. We aimed to compare the induced inflammatory reactions in three keratinocyte cell types—normal human epidermal keratinocytes, the HaCaT cell line and the HPV-KER cell line—upon exposure to the synthetic RNA and DNA analogues poly(I:C) and poly(dA:dT) to reveal the underlying signaling events. Both agents induced the expression of interleukin-6 and tumor necrosis factor α in all cell types; however, notable kinetic and expression level differences were found. Western blot analysis revealed rapid activation of the nuclear factor κB (NF-κB), mitogen activated protein kinase and signal transducers of activator of transcription (STAT) signal transduction pathways in keratinocytes upon poly(I:C) treatment, while poly(dA:dT) induced slower activation. Inhibition of NF-κB, p38, STAT-1 and STAT-3 signaling resulted in decreased cytokine expression, whereas inhibition of mitogen-activated protein kinase kinase 1/2 (MEK1/2) signaling showed a negative feedback role in both poly(I:C)- and poly(dA:dT)-induced cytokine expression. Based on our in vitro results nucleotide fragments are able to induce inflammatory reactions in keratinocytes, but with different rate and kinetics of cytokine expression, explained by faster activation of signaling routes by poly(I:C) than poly(dA:dT).http://www.mdpi.com/1422-0067/19/3/774cytosolic nucleotide fragmentskeratinocytepoly(I:C)poly(dA:dT)signal transduction pathwayinterleukin-6tumor necrosis factor α |
| spellingShingle | Judit Danis Luca Janovák Barbara Gubán Anikó Göblös Kornélia Szabó Lajos Kemény Zsuzsanna Bata-Csörgő Márta Széll Differential Inflammatory-Response Kinetics of Human Keratinocytes upon Cytosolic RNA- and DNA-Fragment Induction International Journal of Molecular Sciences cytosolic nucleotide fragments keratinocyte poly(I:C) poly(dA:dT) signal transduction pathway interleukin-6 tumor necrosis factor α |
| title | Differential Inflammatory-Response Kinetics of Human Keratinocytes upon Cytosolic RNA- and DNA-Fragment Induction |
| title_full | Differential Inflammatory-Response Kinetics of Human Keratinocytes upon Cytosolic RNA- and DNA-Fragment Induction |
| title_fullStr | Differential Inflammatory-Response Kinetics of Human Keratinocytes upon Cytosolic RNA- and DNA-Fragment Induction |
| title_full_unstemmed | Differential Inflammatory-Response Kinetics of Human Keratinocytes upon Cytosolic RNA- and DNA-Fragment Induction |
| title_short | Differential Inflammatory-Response Kinetics of Human Keratinocytes upon Cytosolic RNA- and DNA-Fragment Induction |
| title_sort | differential inflammatory response kinetics of human keratinocytes upon cytosolic rna and dna fragment induction |
| topic | cytosolic nucleotide fragments keratinocyte poly(I:C) poly(dA:dT) signal transduction pathway interleukin-6 tumor necrosis factor α |
| url | http://www.mdpi.com/1422-0067/19/3/774 |
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