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l-Ascorbyl-2-phosphate attenuates NF-κB signaling in SZ95 sebocytes without affecting IL-6 and IL-8 secretion

Acne is the most common inflammatory skin disease. Interleukin-1 (IL-1) is at the beginning of the cytokine signaling cascade and may be involved in the pathogenesis of this disorder. It activates redox-sensitive transcription factors, which induce IL-6 and IL-8 expression. Interestingly, l-ascorbyl...

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Autores principales: Ikeno, Hiroshi, Apel, Mara, Zouboulis, Christos, Luger, Thomas A., Böhm, Markus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4540786/
https://www.ncbi.nlm.nih.gov/pubmed/25894228
http://dx.doi.org/10.1007/s00403-015-1565-z
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author Ikeno, Hiroshi
Apel, Mara
Zouboulis, Christos
Luger, Thomas A.
Böhm, Markus
author_facet Ikeno, Hiroshi
Apel, Mara
Zouboulis, Christos
Luger, Thomas A.
Böhm, Markus
author_sort Ikeno, Hiroshi
collection PubMed
description Acne is the most common inflammatory skin disease. Interleukin-1 (IL-1) is at the beginning of the cytokine signaling cascade and may be involved in the pathogenesis of this disorder. It activates redox-sensitive transcription factors, which induce IL-6 and IL-8 expression. Interestingly, l-ascorbyl-2-phosphate (APS) was shown to have beneficial effects in patients with acne vulgaris. The mechanism of action of this agent remains unknown. Here, we investigated if APS attenuates IL-1β- or TNF-α-mediated IL-6 and IL-8 expression in SZ95 sebocytes, whereas TNF-α was used as control. We also explored NF-κB activation which is known to orchestrate IL-1β- and TNF-α-mediated cytokine expression in many cell types. Both IL-1β and TNF-α increased IL-6 and IL-8 mRNA expression in SZ95 sebocytes. However, only IL-1β induced IL-6 and IL-8 secretion. IL-1β but not TNF-α activated NF-κB canonical signaling as demonstrated by Iκ-Bα phosphorylation and degradation as well as by nuclear accumulation of NF-κB/p65. Concomitant treatment of SZ95 sebocytes with APS attenuated the effect of IL-1β and TNF-α on IL-6 and IL-8 gene expression as well as on IL-1β-mediated NF-κB signaling. In contrast, APS failed to reduce IL-1β-mediated IL-6 and IL-8 secretion, presumably by maintained IL-1β-mediated p38 activation, which is known to control IL-8 secretion. Our findings shed light into the impact of IL-1β on the inflammatory cytokine response and its molecular mechanisms in human sebocytes. Our data further suggest that the beneficial effect of APS in acne patients involves attenuation of NF-κB signaling but not reduction of IL-6 or IL-8 secretion. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00403-015-1565-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-45407862015-08-21 l-Ascorbyl-2-phosphate attenuates NF-κB signaling in SZ95 sebocytes without affecting IL-6 and IL-8 secretion Ikeno, Hiroshi Apel, Mara Zouboulis, Christos Luger, Thomas A. Böhm, Markus Arch Dermatol Res Original Paper Acne is the most common inflammatory skin disease. Interleukin-1 (IL-1) is at the beginning of the cytokine signaling cascade and may be involved in the pathogenesis of this disorder. It activates redox-sensitive transcription factors, which induce IL-6 and IL-8 expression. Interestingly, l-ascorbyl-2-phosphate (APS) was shown to have beneficial effects in patients with acne vulgaris. The mechanism of action of this agent remains unknown. Here, we investigated if APS attenuates IL-1β- or TNF-α-mediated IL-6 and IL-8 expression in SZ95 sebocytes, whereas TNF-α was used as control. We also explored NF-κB activation which is known to orchestrate IL-1β- and TNF-α-mediated cytokine expression in many cell types. Both IL-1β and TNF-α increased IL-6 and IL-8 mRNA expression in SZ95 sebocytes. However, only IL-1β induced IL-6 and IL-8 secretion. IL-1β but not TNF-α activated NF-κB canonical signaling as demonstrated by Iκ-Bα phosphorylation and degradation as well as by nuclear accumulation of NF-κB/p65. Concomitant treatment of SZ95 sebocytes with APS attenuated the effect of IL-1β and TNF-α on IL-6 and IL-8 gene expression as well as on IL-1β-mediated NF-κB signaling. In contrast, APS failed to reduce IL-1β-mediated IL-6 and IL-8 secretion, presumably by maintained IL-1β-mediated p38 activation, which is known to control IL-8 secretion. Our findings shed light into the impact of IL-1β on the inflammatory cytokine response and its molecular mechanisms in human sebocytes. Our data further suggest that the beneficial effect of APS in acne patients involves attenuation of NF-κB signaling but not reduction of IL-6 or IL-8 secretion. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00403-015-1565-z) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2015-04-18 2015 /pmc/articles/PMC4540786/ /pubmed/25894228 http://dx.doi.org/10.1007/s00403-015-1565-z Text en © The Author(s) 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Paper
Ikeno, Hiroshi
Apel, Mara
Zouboulis, Christos
Luger, Thomas A.
Böhm, Markus
l-Ascorbyl-2-phosphate attenuates NF-κB signaling in SZ95 sebocytes without affecting IL-6 and IL-8 secretion
title l-Ascorbyl-2-phosphate attenuates NF-κB signaling in SZ95 sebocytes without affecting IL-6 and IL-8 secretion
title_full l-Ascorbyl-2-phosphate attenuates NF-κB signaling in SZ95 sebocytes without affecting IL-6 and IL-8 secretion
title_fullStr l-Ascorbyl-2-phosphate attenuates NF-κB signaling in SZ95 sebocytes without affecting IL-6 and IL-8 secretion
title_full_unstemmed l-Ascorbyl-2-phosphate attenuates NF-κB signaling in SZ95 sebocytes without affecting IL-6 and IL-8 secretion
title_short l-Ascorbyl-2-phosphate attenuates NF-κB signaling in SZ95 sebocytes without affecting IL-6 and IL-8 secretion
title_sort l-ascorbyl-2-phosphate attenuates nf-κb signaling in sz95 sebocytes without affecting il-6 and il-8 secretion
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4540786/
https://www.ncbi.nlm.nih.gov/pubmed/25894228
http://dx.doi.org/10.1007/s00403-015-1565-z
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