Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Effect of Ultraviolet Radiation on the Expression of Drug Transporters in In Vitro Skin Models

Version 1 : Received: 1 December 2020 / Approved: 2 December 2020 / Online: 2 December 2020 (14:48:32 CET)

How to cite: Barthe, M.; Thénot, J.; Osman-Ponchet, H. Effect of Ultraviolet Radiation on the Expression of Drug Transporters in In Vitro Skin Models. Preprints 2020, 2020120067 (doi: 10.20944/preprints202012.0067.v1). Barthe, M.; Thénot, J.; Osman-Ponchet, H. Effect of Ultraviolet Radiation on the Expression of Drug Transporters in In Vitro Skin Models. Preprints 2020, 2020120067 (doi: 10.20944/preprints202012.0067.v1).

Abstract

The majority of skin cancers are caused by over exposure to ultraviolet (UV) radiation. The effects of UV radiation on the expression of drug transporters expressed in human skin has never been studied. In this the effects of UVA and UVB irradiation on the expression of ATP-binding cassette (ABC) transporters and Solute carrier (SLC) transporters was evaluated in normal human epidermal keratinocytes (NHEK) and normal human dermal fibroblasts (NHDF) in primary culture. First experiments were intended to validate the inflammatory reaction in response to stimulation by lipopolysaccharide (LPS) in NHEK, NHDF and 3D-reconstructed human epidermis (3D-RHE) model. LPS treatment has shown to increase the expression of IL-8 and TNF-alpha in all three in vitro models. Expression of the most expressed ABC and SLC transporters was then measured in NHEK and NHDF after UVA (30 J/m²) and UVB (40 mJ/m²) irradiation. The most striking result was a significant 29-fold increase of the expression of SLCO4A1 in normal human dermal fibroblasts. In summary, this study shows for the first time a significant regulation of the expression of SLCO4A1 in human dermal fibroblasts induced by UVA irradiation. This finding is of particular interest as most of skin cancers are caused by over exposure to ultraviolet radiation and need to be considered in pharmacokinetic evaluation of topical drugs.

Subject Areas

ABC transporters; SLC transporters; in vitro; skin; inflammation; cytokines; UVA; UVB

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