Lead optimization of aryl hydrocarbon receptor ligands for treatment of inflammatory skin disorders

Rikken, Gijs; Smith, Kayla J.; Brink, Noa J.M. van den; Smits, Jos P.H.; Gowda, Krishne; Alnemri, Angela; Kuzu, Gulsum E; Murray, Iain A.; Lin, Jyh-Ming; Smits, J.; Vlijmen-Willems, I.M. van; Amin, Shantu; Perdew, Gary H.; Bogaard, Ellen H. van den

doi:10.1016/j.bcp.2022.115400

Cited by 5 publications

(1 citation statement)

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“…For stimulation experiments, IL–4, IL–13, IL–17A or IL–22 (50 ng/mL per cytokine, Peprotech, Rocky Hill, NJ, USA, 200-04/200-13/200-17/200-22) supplemented with 0.05 % bovine serum albumin (Sigma– Aldrich, A2153) were added to the medium of HEEs of primary keratinocyte from day 5 of air exposure until day 8. AHR ligands (Table S2) were supplemented in the culture medium as previously described (Rikken et al 2023).…”

Section: Methodsmentioning

confidence: 99%

Electrical Impedance Spectroscopy Quantifies Skin Barrier Function in Organotypic In Vitro Epidermis Models

van den Brink,

Pardow,

Meesters

et al. 2024

Preprint

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3 D human epidermal equivalents (HEEs) are a state–of–the–art organotypic culture model in pre–clinical investigative dermatology and regulatory toxicology. Here, we investigated the utility of electrical impedance spectroscopy (EIS) for non–invasive measurement of HEE epidermal barrier function. Our setup comprised a custom–made lid fit with 12 electrode pairs aligned on the standard 24–transwell cell culture system. Serial EIS measurements for seven consecutive days did not impact epidermal morphology and readouts showed comparable trends to HEEs measured only once. We determined two frequency ranges in the resulting impedance spectra: a lower frequency range termed EISdiffcorrelated with keratinocyte terminal differentiation independent of epidermal thickness and a higher frequency range termed EISSCcorrelated withstratum corneumthickness. HEEs generated from CRISPR/Cas9 engineered keratinocytes that lack key differentiation genesFLG,TFAP2A,AHRorCLDN1confirmed that keratinocyte terminal differentiation is the major parameter defining EISdiff. Exposure to pro–inflammatory psoriasis– or atopic dermatitis–associated cytokine cocktails lowered the expression of keratinocyte differentiation markers and reduced EISdiff. This cytokine–associated decrease in EISdiffwas normalized after stimulation with therapeutic molecules. In conclusion, EIS provides a non–invasive system to consecutively and quantitatively assess HEE barrier function and to sensitively and objectively measure barrier development, defects and repair.

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Section: Methodsmentioning

confidence: 99%