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Int. J. Mol. Sci. 2018, 19(3), 774; https://doi.org/10.3390/ijms19030774

Differential Inflammatory-Response Kinetics of Human Keratinocytes upon Cytosolic RNA- and DNA-Fragment Induction

1
Department of Dermatology and Allergology, University of Szeged, 6720 Szeged, Hungary
2
MTA-SZTE Dermatological Research Group, 6720 Szeged, Hungary
3
Department of Medical Genetics, University of Szeged, 6720 Szeged, Hungary
*
Author to whom correspondence should be addressed.
Received: 8 February 2018 / Revised: 27 February 2018 / Accepted: 6 March 2018 / Published: 8 March 2018
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

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). View Full-Text
Keywords: cytosolic nucleotide fragments; keratinocyte; poly(I:C); poly(dA:dT); signal transduction pathway; interleukin-6; tumor necrosis factor α cytosolic nucleotide fragments; keratinocyte; poly(I:C); poly(dA:dT); signal transduction pathway; interleukin-6; tumor necrosis factor α
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Danis, J.; Janovák, L.; Gubán, B.; Göblös, A.; Szabó, K.; Kemény, L.; Bata-Csörgő, Z.; Széll, M. Differential Inflammatory-Response Kinetics of Human Keratinocytes upon Cytosolic RNA- and DNA-Fragment Induction. Int. J. Mol. Sci. 2018, 19, 774.

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