Glycerol Improves Skin Lesion Development in the Imiquimod Mouse Model of Psoriasis: Experimental Confirmation of Anecdotal Reports from Patients with Psoriasis

Glycerol is used in many skin care products because it improves skin function. Anecdotal reports by patients on the National Psoriasis Foundation website also suggest that glycerol may be helpful for the treatment of psoriasis, although to date no experimental data confirm this idea. Glycerol entry...

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Main Authors: Vivek Choudhary, Ismail Kaddour-Djebbar, Victoria E. Custer, Rawipan Uaratanawong, Xunsheng Chen, Elyssa Cohen, Rong Yang, Etsubdenk Ajebo, Sarah Hossack, Wendy B. Bollag
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/16/8749
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author Vivek Choudhary
Ismail Kaddour-Djebbar
Victoria E. Custer
Rawipan Uaratanawong
Xunsheng Chen
Elyssa Cohen
Rong Yang
Etsubdenk Ajebo
Sarah Hossack
Wendy B. Bollag
author_facet Vivek Choudhary
Ismail Kaddour-Djebbar
Victoria E. Custer
Rawipan Uaratanawong
Xunsheng Chen
Elyssa Cohen
Rong Yang
Etsubdenk Ajebo
Sarah Hossack
Wendy B. Bollag
author_sort Vivek Choudhary
collection DOAJ
description Glycerol is used in many skin care products because it improves skin function. Anecdotal reports by patients on the National Psoriasis Foundation website also suggest that glycerol may be helpful for the treatment of psoriasis, although to date no experimental data confirm this idea. Glycerol entry into epidermal keratinocytes is facilitated by aquaglyceroporins like aquaporin-3 (AQP3), and its conversion to phosphatidylglycerol, a lipid messenger that promotes keratinocyte differentiation, requires the lipid-metabolizing enzyme phospholipase-D2 (PLD2). To evaluate whether glycerol inhibits inflammation and psoriasiform lesion development in the imiquimod (IMQ)-induced mouse model of psoriasis, glycerol’s effect on psoriasiform skin lesions was determined in IMQ-treated wild-type and PLD2 knockout mice, with glycerol provided either in drinking water or applied topically. Psoriasis area and severity index, ear thickness and ear biopsy weight, epidermal thickness, and inflammatory markers were quantified. Topical and oral glycerol ameliorated psoriasiform lesion development in wild-type mice. Topical glycerol appeared to act as an emollient to induce beneficial effects, since even in PLD2 knockout mice topical glycerol application improved skin lesions. In contrast, the beneficial effects of oral glycerol required PLD2, with no improvement in psoriasiform lesions observed in PLD2 knockout mice. Our findings suggest that the ability of oral glycerol to improve psoriasiform lesions requires its PLD2-mediated conversion to phosphatidylglycerol, consistent with our previous report that phosphatidylglycerol itself improves psoriasiform lesions in this model. Our data also support anecdotal evidence that glycerol can ameliorate psoriasis symptoms and therefore might be a useful therapy alone or in conjunction with other treatments.
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spelling doaj.art-f2cc6b4e3846440dbc3e29356a7163542023-11-22T07:59:56ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216874910.3390/ijms22168749Glycerol Improves Skin Lesion Development in the Imiquimod Mouse Model of Psoriasis: Experimental Confirmation of Anecdotal Reports from Patients with PsoriasisVivek Choudhary0Ismail Kaddour-Djebbar1Victoria E. Custer2Rawipan Uaratanawong3Xunsheng Chen4Elyssa Cohen5Rong Yang6Etsubdenk Ajebo7Sarah Hossack8Wendy B. Bollag9Charlie Norwood VA Medical Center, Augusta, GA 30904, USACharlie Norwood VA Medical Center, Augusta, GA 30904, USADepartment of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USADepartment of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USADepartment of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USADepartment of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USADepartment of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USADepartment of Dermatology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USADepartment of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USACharlie Norwood VA Medical Center, Augusta, GA 30904, USAGlycerol is used in many skin care products because it improves skin function. Anecdotal reports by patients on the National Psoriasis Foundation website also suggest that glycerol may be helpful for the treatment of psoriasis, although to date no experimental data confirm this idea. Glycerol entry into epidermal keratinocytes is facilitated by aquaglyceroporins like aquaporin-3 (AQP3), and its conversion to phosphatidylglycerol, a lipid messenger that promotes keratinocyte differentiation, requires the lipid-metabolizing enzyme phospholipase-D2 (PLD2). To evaluate whether glycerol inhibits inflammation and psoriasiform lesion development in the imiquimod (IMQ)-induced mouse model of psoriasis, glycerol’s effect on psoriasiform skin lesions was determined in IMQ-treated wild-type and PLD2 knockout mice, with glycerol provided either in drinking water or applied topically. Psoriasis area and severity index, ear thickness and ear biopsy weight, epidermal thickness, and inflammatory markers were quantified. Topical and oral glycerol ameliorated psoriasiform lesion development in wild-type mice. Topical glycerol appeared to act as an emollient to induce beneficial effects, since even in PLD2 knockout mice topical glycerol application improved skin lesions. In contrast, the beneficial effects of oral glycerol required PLD2, with no improvement in psoriasiform lesions observed in PLD2 knockout mice. Our findings suggest that the ability of oral glycerol to improve psoriasiform lesions requires its PLD2-mediated conversion to phosphatidylglycerol, consistent with our previous report that phosphatidylglycerol itself improves psoriasiform lesions in this model. Our data also support anecdotal evidence that glycerol can ameliorate psoriasis symptoms and therefore might be a useful therapy alone or in conjunction with other treatments.https://www.mdpi.com/1422-0067/22/16/8749aquaporin-3 (AQP3)phospholipase D2 (PLD2)epidermisglycerolimiquimod (IMQ)keratinocytes
spellingShingle Vivek Choudhary
Ismail Kaddour-Djebbar
Victoria E. Custer
Rawipan Uaratanawong
Xunsheng Chen
Elyssa Cohen
Rong Yang
Etsubdenk Ajebo
Sarah Hossack
Wendy B. Bollag
Glycerol Improves Skin Lesion Development in the Imiquimod Mouse Model of Psoriasis: Experimental Confirmation of Anecdotal Reports from Patients with Psoriasis
International Journal of Molecular Sciences
aquaporin-3 (AQP3)
phospholipase D2 (PLD2)
epidermis
glycerol
imiquimod (IMQ)
keratinocytes
title Glycerol Improves Skin Lesion Development in the Imiquimod Mouse Model of Psoriasis: Experimental Confirmation of Anecdotal Reports from Patients with Psoriasis
title_full Glycerol Improves Skin Lesion Development in the Imiquimod Mouse Model of Psoriasis: Experimental Confirmation of Anecdotal Reports from Patients with Psoriasis
title_fullStr Glycerol Improves Skin Lesion Development in the Imiquimod Mouse Model of Psoriasis: Experimental Confirmation of Anecdotal Reports from Patients with Psoriasis
title_full_unstemmed Glycerol Improves Skin Lesion Development in the Imiquimod Mouse Model of Psoriasis: Experimental Confirmation of Anecdotal Reports from Patients with Psoriasis
title_short Glycerol Improves Skin Lesion Development in the Imiquimod Mouse Model of Psoriasis: Experimental Confirmation of Anecdotal Reports from Patients with Psoriasis
title_sort glycerol improves skin lesion development in the imiquimod mouse model of psoriasis experimental confirmation of anecdotal reports from patients with psoriasis
topic aquaporin-3 (AQP3)
phospholipase D2 (PLD2)
epidermis
glycerol
imiquimod (IMQ)
keratinocytes
url https://www.mdpi.com/1422-0067/22/16/8749
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