The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.
Coal tar induces AHR-dependent skin barrier repair in atopic dermatitis
Open accessAbstract
Topical application of coal tar is one of the oldest therapies for atopic dermatitis (AD), a T helper 2 (Th2) lymphocyte-mediated skin disease associated with loss-of-function mutations in the skin barrier gene, filaggrin (FLG). Despite its longstanding clinical use and efficacy, the molecular mechanism of coal tar therapy is unknown. Using organotypic skin models with primary keratinocytes from AD patients and controls, we found that coal tar activated the aryl hydrocarbon receptor (AHR), resulting in induction of epidermal differentiation. AHR knockdown by siRNA completely abrogated this effect. Coal tar restored filaggrin expression in FLG-haploinsufficient keratinocytes to wild-type levels, and counteracted Th2 cytokine-mediated downregulation of skin barrier proteins. In AD patients, coal tar completely restored expression of major skin barrier proteins, including filaggrin. Using organotypic skin models stimulated with Th2 cytokines IL-4 and IL-13, we found coal tar to diminish spongiosis, apoptosis, and CCL26 expression, all AD hallmarks. Coal tar interfered with Th2 cytokine signaling via dephosphorylation of STAT6, most likely due to AHR-regulated activation of the NRF2 antioxidative stress pathway. The therapeutic effect of AHR activation herein described opens a new avenue to reconsider AHR as a pharmacological target and could lead to the development of mechanism-based drugs for AD.
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“Interestingly, coal tar has been shown to bind to AhR and to restore the expression of filaggrin, as shown by immunohistochemistry and transcriptomic analysis59.”
From Atopic dermatitis: an expanding therapeutic pipeline for a complex disease (2022) · cites this paper as [59]
In the citing paper
“Activation of NRF2 by AHR ligands such as coal tar abolished IL-4/IL-13–mediated inhibition of epidermal barrier proteins such as FLG and LOR (42, 56).”
From Particulate matter causes skin barrier dysfunction. (2021) · cites this paper as [56]
Citations
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Sorted by citations
Guidelines of care for the management of atopic dermatitis
Eichenfield, L. F., Tom, W. L., Chamlin, S. L., Feldman, S. R., Hanifin, J. M., Simpson, E. L., Berger, T. G., Bergman, J. N., Cohen, D. E., Cooper, K. D., et al. (2013) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2013.10.010 · Cited by 1,305
Guidelines of care for the management of atopic dermatitis
Eichenfield, L. F., Tom, W. L., Berger, T. G., Krol, A. L., Paller, A. S., Schwarzenberger, K., Bergman, J. N., Chamlin, S. L., Cohen, D. E., Cooper, K. D., et al. (2014) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2014.03.023 · Cited by 1,220
The aryl hydrocarbon receptor: multitasking in the immune system
Stockinger, B., Meglio, P. D., Gialitakis, M., & Duarte, J. H. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120245 · Cited by 909
Aryl hydrocarbon receptor ligands in cancer: friend and foe
Murray, I. A., Patterson, A. D., & Perdew, G. H. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3846 · Cited by 916
Atopic dermatitis: an expanding therapeutic pipeline for a complex disease
Bieber, T. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00266-6 · Cited by 623
Metadata
- Authors
- van den Bogaard, E. H., Bergboer, J. G. M., Vonk-Bergers, M., van Vlijmen-Willems, I. M. J. J., Hato, S. V., van der Valk, P. G. M., Schröder, J. M., Joosten, I., Zeeuwen, P. L. J. M., & Schalkwijk, J.
- Affiliations
- Radboud University Medical Center (NL)
- University Hospital Schleswig-Holstein (DE)
- Radboud University Nijmegen (NL)
- Venue
- Journal of Clinical Investigation
- Published
- 2013-01-25
- Volume
- 123
- Issue
- 2
- Pages
- 917-27
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3561798
- OpenAlex
- W2047893094
- Cited by
- 373
- References
- 64
- Citations by year
- 2026: 15 · 2025: 21 · 2024: 36 · 2023: 31 · 2022: 38 · 2021: 33 · 2020: 34 · 2019: 25 · 2018: 33 · 2017: 30 · 2016: 18 · 2015: 19 · 2014: 28 · 2013: 12
- FWCI
- 30.00
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Keywords
- coal tar, atopic dermatitis, aryl hydrocarbon receptor, skin barrier repair, filaggrin, Th2 cytokines, IL-4, IL-13, Nrf2 signaling, epidermal differentiation, keratinocytes, spongiosis, CCL26, organotypic skin model
- MeSH terms
- Filaggrin Proteins, Administration, Topical, Cell Differentiation, Cells, Cultured, Coal Tar, Dermatitis, Atopic, Humans, Intermediate Filament Proteins, Models, Biological, Signal Transduction, Keratinocytes, Up-Regulation, Cytokines, Receptors, Aryl Hydrocarbon, Oxidative Stress, Th2 Cells, RNA, Small Interfering, NF-E2-Related Factor 2
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