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42 Polyprenol Could Prevent Loss of Filaggrin in Epithelial Cells in Atopic Dermatitis

BACKGROUND: In epithelial cells loss of filaggrin correlates with atopic dermatitis (AD) presence and activity. Dysregulation of DPAGT1 (Dolichyl-phosphate (UDP-N-acetylglucosamine) N-acetylglucosaminephosphotransferase 1 (GlcNAc-1-P transferase) causes disturbances in filaggrin expression. The rese...

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Autores principales: Kuznecovs, Ivans S., Joksta, Inese, Kuznecovs, Sergejs, Kuznecovac, Galina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: World Allergy Organization Journal 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3513015/
http://dx.doi.org/10.1097/01.WOX.0000411787.97837.23
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author Kuznecovs, Ivans S.
Joksta, Inese
Kuznecovs, Sergejs
Kuznecovac, Galina
author_facet Kuznecovs, Ivans S.
Joksta, Inese
Kuznecovs, Sergejs
Kuznecovac, Galina
author_sort Kuznecovs, Ivans S.
collection PubMed
description BACKGROUND: In epithelial cells loss of filaggrin correlates with atopic dermatitis (AD) presence and activity. Dysregulation of DPAGT1 (Dolichyl-phosphate (UDP-N-acetylglucosamine) N-acetylglucosaminephosphotransferase 1 (GlcNAc-1-P transferase) causes disturbances in filaggrin expression. The resent results are in favour of the idea that N-glycosylation in keratinocytes cells is limited by Dolichyl Phosphate Cycle (DPC) intermediates. The aim of the present study is to investigate the effect of Polyprenol (PP), which provides a dolichol phosphate (DolP) substitute on regulation of filaggrin expression. METHODS: Filaggrin expression was measured in skin biopsies from 42 persons with AD and 36 with normal skin and cultured keratinocytes; PP concentration in the culture medium made up 10(−2) to 10(−6). Immunohistochemical and Western blotting methods were used to detect the changes in the expression levels of filaggrin and DPAGT1. IL-4 and IL-13 was determined using ELISA. Intermediates of DPC fractions were analysed by HPLC method. RESULTS: Overexpression of DPAGT1 was 5-fold higher in AD skin biopsies than in normal skin biopsies. AD cells differ from normal one in filaggrin content lost by 3 to 4 times. IL-4 and IL-13 cause overexpression and abberant N-glycosylation of filaggrin in DPC. The study showed overexpression of DPAGT1 and 6-fold DPC intermediates decrease in keratinocytes in presence of IL-13 and 2-fold in presence of IL-4 cells. Treatment of keratinocytes with PP resulted in downregulation of DPAGT1. It is established that PP in the concentration 10(−2) M could overcome DPAGT1 overexpression which leads to regulation of filaggrin N-glycosylation. CONCLUSIONS: IL-13 could cause DPAGT overexpression and dysregulation of N-glycosylation in keratinocytes which leads to AD fenotype affecting the stability of tight assembly and adherence junctions in skin. The findings indicate that DPAGT1 overexpression in keratinocytes treated with IL-4 and IL-13 can be overcomed by PP, which provides a DolP substitute for DPAGT1 normal expression, N-glycosylation and filaggrin loss prevention without neutralization of interleukins. Polyprenol could be a promising agent for atopic dermatis prevention and control.
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spelling pubmed-35130152012-12-21 42 Polyprenol Could Prevent Loss of Filaggrin in Epithelial Cells in Atopic Dermatitis Kuznecovs, Ivans S. Joksta, Inese Kuznecovs, Sergejs Kuznecovac, Galina World Allergy Organ J Abstracts of the XXII World Allergy Congress BACKGROUND: In epithelial cells loss of filaggrin correlates with atopic dermatitis (AD) presence and activity. Dysregulation of DPAGT1 (Dolichyl-phosphate (UDP-N-acetylglucosamine) N-acetylglucosaminephosphotransferase 1 (GlcNAc-1-P transferase) causes disturbances in filaggrin expression. The resent results are in favour of the idea that N-glycosylation in keratinocytes cells is limited by Dolichyl Phosphate Cycle (DPC) intermediates. The aim of the present study is to investigate the effect of Polyprenol (PP), which provides a dolichol phosphate (DolP) substitute on regulation of filaggrin expression. METHODS: Filaggrin expression was measured in skin biopsies from 42 persons with AD and 36 with normal skin and cultured keratinocytes; PP concentration in the culture medium made up 10(−2) to 10(−6). Immunohistochemical and Western blotting methods were used to detect the changes in the expression levels of filaggrin and DPAGT1. IL-4 and IL-13 was determined using ELISA. Intermediates of DPC fractions were analysed by HPLC method. RESULTS: Overexpression of DPAGT1 was 5-fold higher in AD skin biopsies than in normal skin biopsies. AD cells differ from normal one in filaggrin content lost by 3 to 4 times. IL-4 and IL-13 cause overexpression and abberant N-glycosylation of filaggrin in DPC. The study showed overexpression of DPAGT1 and 6-fold DPC intermediates decrease in keratinocytes in presence of IL-13 and 2-fold in presence of IL-4 cells. Treatment of keratinocytes with PP resulted in downregulation of DPAGT1. It is established that PP in the concentration 10(−2) M could overcome DPAGT1 overexpression which leads to regulation of filaggrin N-glycosylation. CONCLUSIONS: IL-13 could cause DPAGT overexpression and dysregulation of N-glycosylation in keratinocytes which leads to AD fenotype affecting the stability of tight assembly and adherence junctions in skin. The findings indicate that DPAGT1 overexpression in keratinocytes treated with IL-4 and IL-13 can be overcomed by PP, which provides a DolP substitute for DPAGT1 normal expression, N-glycosylation and filaggrin loss prevention without neutralization of interleukins. Polyprenol could be a promising agent for atopic dermatis prevention and control. World Allergy Organization Journal 2012-02-17 /pmc/articles/PMC3513015/ http://dx.doi.org/10.1097/01.WOX.0000411787.97837.23 Text en Copyright © 2012 by World Allergy Organization
spellingShingle Abstracts of the XXII World Allergy Congress
Kuznecovs, Ivans S.
Joksta, Inese
Kuznecovs, Sergejs
Kuznecovac, Galina
42 Polyprenol Could Prevent Loss of Filaggrin in Epithelial Cells in Atopic Dermatitis
title 42 Polyprenol Could Prevent Loss of Filaggrin in Epithelial Cells in Atopic Dermatitis
title_full 42 Polyprenol Could Prevent Loss of Filaggrin in Epithelial Cells in Atopic Dermatitis
title_fullStr 42 Polyprenol Could Prevent Loss of Filaggrin in Epithelial Cells in Atopic Dermatitis
title_full_unstemmed 42 Polyprenol Could Prevent Loss of Filaggrin in Epithelial Cells in Atopic Dermatitis
title_short 42 Polyprenol Could Prevent Loss of Filaggrin in Epithelial Cells in Atopic Dermatitis
title_sort 42 polyprenol could prevent loss of filaggrin in epithelial cells in atopic dermatitis
topic Abstracts of the XXII World Allergy Congress
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3513015/
http://dx.doi.org/10.1097/01.WOX.0000411787.97837.23
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