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T Helper 1 and T Helper 2 Cytokines Differentially Modulate Expression of Filaggrin and its Processing Proteases in Human Keratinocytes
BACKGROUND: Atopic dermatitis (AD) is characterized by defective skin barrier and imbalance in T helper 1/T helper 2 (Th1/Th2) cytokine expression. Filaggrin (FLG) is the key protein to maintaining skin barrier function. Recent studies indicated that Th1/Th2 cytokines influence FLG expression in ker...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Medknow Publications & Media Pvt Ltd
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4799573/ https://www.ncbi.nlm.nih.gov/pubmed/26831231 http://dx.doi.org/10.4103/0366-6999.174489 |
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author | Di, Zheng-Hong Ma, Lei Qi, Rui-Qun Sun, Xiao-Dong Huo, Wei Zhang, Li Lyu, Ya-Ni Hong, Yu-Xiao Chen, Hong-Duo Gao, Xing-Hua |
author_facet | Di, Zheng-Hong Ma, Lei Qi, Rui-Qun Sun, Xiao-Dong Huo, Wei Zhang, Li Lyu, Ya-Ni Hong, Yu-Xiao Chen, Hong-Duo Gao, Xing-Hua |
author_sort | Di, Zheng-Hong |
collection | PubMed |
description | BACKGROUND: Atopic dermatitis (AD) is characterized by defective skin barrier and imbalance in T helper 1/T helper 2 (Th1/Th2) cytokine expression. Filaggrin (FLG) is the key protein to maintaining skin barrier function. Recent studies indicated that Th1/Th2 cytokines influence FLG expression in keratinocytes. However, the role of Th1/Th2 cytokines on FLG processing is not substantially documented. Our aim was to investigate the impact of Th1/Th2 cytokines on FLG processing. METHODS: HaCaT cells and normal human keratinocytes were cultured in low and high calcium media and stimulated by either interleukin (IL)-4, 13 or interferon-γ (IFN-γ). FLG, its major processing proteases and key protease inhibitor lymphoepithelial Kazal-type-related inhibitor (LEKTI) were measured by both real-time quantitative polymerase chain reaction and Western blotting. Their expression was also evaluated in acute and chronic AD lesions by immunohistochemistry. RESULTS: IL-4/13 significantly reduced, while IFN-γ significantly up-regulated FLG expression. IL-4/13 significantly increased, whereas IFN-γ significantly decreased the expression of kallikreins 5 and 7, matriptase and channel-activating serine protease 1. On the contrary, IL-4/13 significantly decreased, while IFN-γ increased the expression of LEKTI and caspase-14. Similar trends were observed in AD lesions. CONCLUSIONS: Our results suggested that Th1/Th2 cytokines differentially regulated the expression of major FLG processing enzymes. The imbalance between Th1 and Th2 polarized immune response seems to extend to FLG homeostasis, through the network of FLG processing enzymes. |
format | Online Article Text |
id | pubmed-4799573 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Medknow Publications & Media Pvt Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-47995732016-04-04 T Helper 1 and T Helper 2 Cytokines Differentially Modulate Expression of Filaggrin and its Processing Proteases in Human Keratinocytes Di, Zheng-Hong Ma, Lei Qi, Rui-Qun Sun, Xiao-Dong Huo, Wei Zhang, Li Lyu, Ya-Ni Hong, Yu-Xiao Chen, Hong-Duo Gao, Xing-Hua Chin Med J (Engl) Original Article BACKGROUND: Atopic dermatitis (AD) is characterized by defective skin barrier and imbalance in T helper 1/T helper 2 (Th1/Th2) cytokine expression. Filaggrin (FLG) is the key protein to maintaining skin barrier function. Recent studies indicated that Th1/Th2 cytokines influence FLG expression in keratinocytes. However, the role of Th1/Th2 cytokines on FLG processing is not substantially documented. Our aim was to investigate the impact of Th1/Th2 cytokines on FLG processing. METHODS: HaCaT cells and normal human keratinocytes were cultured in low and high calcium media and stimulated by either interleukin (IL)-4, 13 or interferon-γ (IFN-γ). FLG, its major processing proteases and key protease inhibitor lymphoepithelial Kazal-type-related inhibitor (LEKTI) were measured by both real-time quantitative polymerase chain reaction and Western blotting. Their expression was also evaluated in acute and chronic AD lesions by immunohistochemistry. RESULTS: IL-4/13 significantly reduced, while IFN-γ significantly up-regulated FLG expression. IL-4/13 significantly increased, whereas IFN-γ significantly decreased the expression of kallikreins 5 and 7, matriptase and channel-activating serine protease 1. On the contrary, IL-4/13 significantly decreased, while IFN-γ increased the expression of LEKTI and caspase-14. Similar trends were observed in AD lesions. CONCLUSIONS: Our results suggested that Th1/Th2 cytokines differentially regulated the expression of major FLG processing enzymes. The imbalance between Th1 and Th2 polarized immune response seems to extend to FLG homeostasis, through the network of FLG processing enzymes. Medknow Publications & Media Pvt Ltd 2016-02-05 /pmc/articles/PMC4799573/ /pubmed/26831231 http://dx.doi.org/10.4103/0366-6999.174489 Text en Copyright: © 2016 Chinese Medical Journal http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. |
spellingShingle | Original Article Di, Zheng-Hong Ma, Lei Qi, Rui-Qun Sun, Xiao-Dong Huo, Wei Zhang, Li Lyu, Ya-Ni Hong, Yu-Xiao Chen, Hong-Duo Gao, Xing-Hua T Helper 1 and T Helper 2 Cytokines Differentially Modulate Expression of Filaggrin and its Processing Proteases in Human Keratinocytes |
title | T Helper 1 and T Helper 2 Cytokines Differentially Modulate Expression of Filaggrin and its Processing Proteases in Human Keratinocytes |
title_full | T Helper 1 and T Helper 2 Cytokines Differentially Modulate Expression of Filaggrin and its Processing Proteases in Human Keratinocytes |
title_fullStr | T Helper 1 and T Helper 2 Cytokines Differentially Modulate Expression of Filaggrin and its Processing Proteases in Human Keratinocytes |
title_full_unstemmed | T Helper 1 and T Helper 2 Cytokines Differentially Modulate Expression of Filaggrin and its Processing Proteases in Human Keratinocytes |
title_short | T Helper 1 and T Helper 2 Cytokines Differentially Modulate Expression of Filaggrin and its Processing Proteases in Human Keratinocytes |
title_sort | t helper 1 and t helper 2 cytokines differentially modulate expression of filaggrin and its processing proteases in human keratinocytes |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4799573/ https://www.ncbi.nlm.nih.gov/pubmed/26831231 http://dx.doi.org/10.4103/0366-6999.174489 |
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