Isosorbide Fatty Acid Diesters Have Synergistic Anti-Inflammatory Effects in Cytokine-Induced Tissue Culture Models of Atopic Dermatitis
Atopic dermatitis (AD) is a chronic disease in which epidermal barrier disruption triggers Th2-mediated eruption of eczematous lesions. Topical emollients are a cornerstone of chronic management. This study evaluated efficacy of two plant-derived oil derivatives, isosorbide di-(linoleate/oleate) (ID...
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/22/14307 |
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| author | William R. Swindell Krzysztof Bojanowski Ratan K. Chaudhuri |
| author_facet | William R. Swindell Krzysztof Bojanowski Ratan K. Chaudhuri |
| author_sort | William R. Swindell |
| collection | DOAJ |
| description | Atopic dermatitis (AD) is a chronic disease in which epidermal barrier disruption triggers Th2-mediated eruption of eczematous lesions. Topical emollients are a cornerstone of chronic management. This study evaluated efficacy of two plant-derived oil derivatives, isosorbide di-(linoleate/oleate) (IDL) and isosorbide dicaprylate (IDC), using AD-like tissue culture models. Treatment of reconstituted human epidermis with cytokine cocktail (IL-4 + IL-13 + TNF-α + IL-31) compromised the epidermal barrier, but this was prevented by co-treatment with IDL and IDC. Cytokine stimulation also dysregulated expression of keratinocyte (KC) differentiation genes whereas treatment with IDC or IDL + IDC up-regulated genes associated with early (but not late) KC differentiation. Although neither IDL nor IDC inhibited Th2 cytokine responses, both compounds repressed TNF-α-induced genes and IDL + IDC led to synergistic down-regulation of inflammatory (<i>IL1B</i>, <i>ITGA5</i>) and neurogenic pruritus (<i>TRPA1</i>) mediators. Treatment of cytokine-stimulated skin explants with IDC decreased lactate dehydrogenase (LDH) secretion by more than 50% (more than observed with cyclosporine) and in vitro LDH activity was inhibited by IDL and IDC. These results demonstrate anti-inflammatory mechanisms of isosorbide fatty acid diesters in AD-like skin models. Our findings highlight the multifunctional potential of plant oil derivatives as topical ingredients and support studies of IDL and IDC as therapeutic candidates. |
| first_indexed | 2024-03-09T18:15:22Z |
| format | Article |
| id | doaj.art-0ca5984235f543b4be2765b7dc5e469b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T18:15:22Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0ca5984235f543b4be2765b7dc5e469b2023-11-24T08:42:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221430710.3390/ijms232214307Isosorbide Fatty Acid Diesters Have Synergistic Anti-Inflammatory Effects in Cytokine-Induced Tissue Culture Models of Atopic DermatitisWilliam R. Swindell0Krzysztof Bojanowski1Ratan K. Chaudhuri2Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USASunny BioDiscovery Inc., Santa Paula, CA 93060, USASytheon Ltd., Parsippany, NJ 07054, USAAtopic dermatitis (AD) is a chronic disease in which epidermal barrier disruption triggers Th2-mediated eruption of eczematous lesions. Topical emollients are a cornerstone of chronic management. This study evaluated efficacy of two plant-derived oil derivatives, isosorbide di-(linoleate/oleate) (IDL) and isosorbide dicaprylate (IDC), using AD-like tissue culture models. Treatment of reconstituted human epidermis with cytokine cocktail (IL-4 + IL-13 + TNF-α + IL-31) compromised the epidermal barrier, but this was prevented by co-treatment with IDL and IDC. Cytokine stimulation also dysregulated expression of keratinocyte (KC) differentiation genes whereas treatment with IDC or IDL + IDC up-regulated genes associated with early (but not late) KC differentiation. Although neither IDL nor IDC inhibited Th2 cytokine responses, both compounds repressed TNF-α-induced genes and IDL + IDC led to synergistic down-regulation of inflammatory (<i>IL1B</i>, <i>ITGA5</i>) and neurogenic pruritus (<i>TRPA1</i>) mediators. Treatment of cytokine-stimulated skin explants with IDC decreased lactate dehydrogenase (LDH) secretion by more than 50% (more than observed with cyclosporine) and in vitro LDH activity was inhibited by IDL and IDC. These results demonstrate anti-inflammatory mechanisms of isosorbide fatty acid diesters in AD-like skin models. Our findings highlight the multifunctional potential of plant oil derivatives as topical ingredients and support studies of IDL and IDC as therapeutic candidates.https://www.mdpi.com/1422-0067/23/22/14307atopic dermatitisdrug developmentemollientisosorbide diestershypersensitivitymoisturizer |
| spellingShingle | William R. Swindell Krzysztof Bojanowski Ratan K. Chaudhuri Isosorbide Fatty Acid Diesters Have Synergistic Anti-Inflammatory Effects in Cytokine-Induced Tissue Culture Models of Atopic Dermatitis International Journal of Molecular Sciences atopic dermatitis drug development emollient isosorbide diesters hypersensitivity moisturizer |
| title | Isosorbide Fatty Acid Diesters Have Synergistic Anti-Inflammatory Effects in Cytokine-Induced Tissue Culture Models of Atopic Dermatitis |
| title_full | Isosorbide Fatty Acid Diesters Have Synergistic Anti-Inflammatory Effects in Cytokine-Induced Tissue Culture Models of Atopic Dermatitis |
| title_fullStr | Isosorbide Fatty Acid Diesters Have Synergistic Anti-Inflammatory Effects in Cytokine-Induced Tissue Culture Models of Atopic Dermatitis |
| title_full_unstemmed | Isosorbide Fatty Acid Diesters Have Synergistic Anti-Inflammatory Effects in Cytokine-Induced Tissue Culture Models of Atopic Dermatitis |
| title_short | Isosorbide Fatty Acid Diesters Have Synergistic Anti-Inflammatory Effects in Cytokine-Induced Tissue Culture Models of Atopic Dermatitis |
| title_sort | isosorbide fatty acid diesters have synergistic anti inflammatory effects in cytokine induced tissue culture models of atopic dermatitis |
| topic | atopic dermatitis drug development emollient isosorbide diesters hypersensitivity moisturizer |
| url | https://www.mdpi.com/1422-0067/23/22/14307 |
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