TNF-α and Th2 cytokines induce atopic dermatitis–like features on epidermal differentiation proteins and stratum corneum lipids in human skin equivalents
Atopic dermatitis (AD) is a chronic inflammatory skin disease in which the skin barrier function is disrupted. In this inflammatory AD environment, cytokines are upregulated, but the cytokine effect on the AD skin barrier is not fully understood. We aimed to investigate the influence of Th2 (IL-4, I...
| Asıl Yazarlar: | , , , , , , , |
|---|---|
| Materyal Türü: | Journal article |
| Dil: | English |
| Baskı/Yayın Bilgisi: |
Elsevier
2014
|
| _version_ | 1826316113164632064 |
|---|---|
| author | Danso, MO Van Drongelen, V Mulder, A Van Esch, J Scott, H Van Smeden, J El Ghalbzouri, A Bouwstra, JA |
| author_facet | Danso, MO Van Drongelen, V Mulder, A Van Esch, J Scott, H Van Smeden, J El Ghalbzouri, A Bouwstra, JA |
| author_sort | Danso, MO |
| collection | OXFORD |
| description | Atopic dermatitis (AD) is a chronic inflammatory skin disease in which the skin barrier function is disrupted. In this inflammatory AD environment, cytokines are upregulated, but the cytokine effect on the AD skin barrier is not fully understood. We aimed to investigate the influence of Th2 (IL-4, IL-13, IL-31) and pro-inflammatory (tumor necrosis factor alpha (TNF-α)) cytokines on epidermal morphogenesis, proliferation, differentiation, and stratum corneum lipid properties. For this purpose, we used the Leiden epidermal model (LEM) in which the medium was supplemented with these cytokines. Our results show that IL-4, IL-13, IL-31, and TNF-α induce spongiosis, augment TSLP secretion by keratinocytes, and alter early and terminal differentiation-protein expression in LEMs. TNF-α alone or in combination with Th2 cytokines decreases the level of long chain free fatty acids (FFAs) and ester linked ω-hydroxy (EO) ceramides, consequently affecting the lipid organization. IL-31 increases long chain FFAs in LEMs but decreases relative abundance of EO ceramides. These findings clearly show that supplementation with TNF-α and Th2 cytokines influence epidermal morphogenesis and barrier function. As a result, these LEMs show similar characteristics as found in AD skin and can be used as an excellent tool for screening formulations and drugs for the treatment of AD. |
| first_indexed | 2024-12-09T03:37:50Z |
| format | Journal article |
| id | oxford-uuid:dcc25ee8-e67f-4a42-9bf2-f6152d27b676 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:37:50Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:dcc25ee8-e67f-4a42-9bf2-f6152d27b6762024-12-04T11:42:08ZTNF-α and Th2 cytokines induce atopic dermatitis–like features on epidermal differentiation proteins and stratum corneum lipids in human skin equivalentsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:dcc25ee8-e67f-4a42-9bf2-f6152d27b676EnglishSymplectic Elements at OxfordElsevier2014Danso, MOVan Drongelen, VMulder, AVan Esch, JScott, HVan Smeden, JEl Ghalbzouri, ABouwstra, JAAtopic dermatitis (AD) is a chronic inflammatory skin disease in which the skin barrier function is disrupted. In this inflammatory AD environment, cytokines are upregulated, but the cytokine effect on the AD skin barrier is not fully understood. We aimed to investigate the influence of Th2 (IL-4, IL-13, IL-31) and pro-inflammatory (tumor necrosis factor alpha (TNF-α)) cytokines on epidermal morphogenesis, proliferation, differentiation, and stratum corneum lipid properties. For this purpose, we used the Leiden epidermal model (LEM) in which the medium was supplemented with these cytokines. Our results show that IL-4, IL-13, IL-31, and TNF-α induce spongiosis, augment TSLP secretion by keratinocytes, and alter early and terminal differentiation-protein expression in LEMs. TNF-α alone or in combination with Th2 cytokines decreases the level of long chain free fatty acids (FFAs) and ester linked ω-hydroxy (EO) ceramides, consequently affecting the lipid organization. IL-31 increases long chain FFAs in LEMs but decreases relative abundance of EO ceramides. These findings clearly show that supplementation with TNF-α and Th2 cytokines influence epidermal morphogenesis and barrier function. As a result, these LEMs show similar characteristics as found in AD skin and can be used as an excellent tool for screening formulations and drugs for the treatment of AD. |
| spellingShingle | Danso, MO Van Drongelen, V Mulder, A Van Esch, J Scott, H Van Smeden, J El Ghalbzouri, A Bouwstra, JA TNF-α and Th2 cytokines induce atopic dermatitis–like features on epidermal differentiation proteins and stratum corneum lipids in human skin equivalents |
| title | TNF-α and Th2 cytokines induce atopic dermatitis–like features on epidermal differentiation proteins and stratum corneum lipids in human skin equivalents |
| title_full | TNF-α and Th2 cytokines induce atopic dermatitis–like features on epidermal differentiation proteins and stratum corneum lipids in human skin equivalents |
| title_fullStr | TNF-α and Th2 cytokines induce atopic dermatitis–like features on epidermal differentiation proteins and stratum corneum lipids in human skin equivalents |
| title_full_unstemmed | TNF-α and Th2 cytokines induce atopic dermatitis–like features on epidermal differentiation proteins and stratum corneum lipids in human skin equivalents |
| title_short | TNF-α and Th2 cytokines induce atopic dermatitis–like features on epidermal differentiation proteins and stratum corneum lipids in human skin equivalents |
| title_sort | tnf α and th2 cytokines induce atopic dermatitis like features on epidermal differentiation proteins and stratum corneum lipids in human skin equivalents |
| work_keys_str_mv | AT dansomo tnfaandth2cytokinesinduceatopicdermatitislikefeaturesonepidermaldifferentiationproteinsandstratumcorneumlipidsinhumanskinequivalents AT vandrongelenv tnfaandth2cytokinesinduceatopicdermatitislikefeaturesonepidermaldifferentiationproteinsandstratumcorneumlipidsinhumanskinequivalents AT muldera tnfaandth2cytokinesinduceatopicdermatitislikefeaturesonepidermaldifferentiationproteinsandstratumcorneumlipidsinhumanskinequivalents AT vaneschj tnfaandth2cytokinesinduceatopicdermatitislikefeaturesonepidermaldifferentiationproteinsandstratumcorneumlipidsinhumanskinequivalents AT scotth tnfaandth2cytokinesinduceatopicdermatitislikefeaturesonepidermaldifferentiationproteinsandstratumcorneumlipidsinhumanskinequivalents AT vansmedenj tnfaandth2cytokinesinduceatopicdermatitislikefeaturesonepidermaldifferentiationproteinsandstratumcorneumlipidsinhumanskinequivalents AT elghalbzouria tnfaandth2cytokinesinduceatopicdermatitislikefeaturesonepidermaldifferentiationproteinsandstratumcorneumlipidsinhumanskinequivalents AT bouwstraja tnfaandth2cytokinesinduceatopicdermatitislikefeaturesonepidermaldifferentiationproteinsandstratumcorneumlipidsinhumanskinequivalents |