title: Increased permeability of reconstructed human epidermis from UVB-irradiated keratinocytes.
abstract: Extrinsic (photo) aging accelerates chronologically aging in the skin due to cumulative UV irradiation. Despite recent insights into the molecular mechanisms of fibroblast aging, age-related changes of the skin barrier function have been understudied. In contrast, the constantly increasing subpopulation of aged patients causes a clinical need for effective and safe (dermatological) treatment. Herein, we reconstructed human epidermis from UVB-irradiated keratinocytes (UVB-RHE). UVB-irradiated keratinocytes show higher activity of senescence associated β-galactosidase, less cell proliferation, and reduced viability. Higher amounts of β-galactosidase are also detectable in UVB-RHE. Moreover, UVB-RHE release more interleukin-1α and -8 into the culture medium and present altered differentiation with a thinner stratum corneum compared to normal RHE. For the first time, the permeation of testosterone and caffeine through UVB-irradiated RHE indicate a clear influence of the UVB stress on the skin barrier function. Impaired barrier function was confirmed by the increased permeation of testosterone and caffeine as well as by the increased penetration of dendritic core-multishell nanocarriers into the constructs. Taken together, UVB-RHE emulate hallmarks of skin aging and might contribute to an improved non-clinical development of medicinal or cosmetic products.
authors.affiliation: Institute for Pharmacy, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany.
authors.forename: Lilian Julia
authors.initials: LJ
authors.lastname: Löwenau
authors.affiliation: Institute for Pharmacy, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Zoschke
authors.affiliation: Institute of Experimental Physics, Freie Universität Berlin, Arnimallee 14, 14195 Berlin, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Brodwolf
authors.affiliation: Institute of Experimental Physics, Freie Universität Berlin, Arnimallee 14, 14195 Berlin, Germany.
authors.forename: Pierre
authors.initials: P
authors.lastname: Volz
authors.affiliation: Institute for Pharmacy, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hausmann
authors.affiliation: Institute for Pharmacy, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany.
authors.forename: Suvara
authors.initials: S
authors.lastname: Wattanapitayakul
authors.affiliation: Institute of Experimental Physics, Freie Universität Berlin, Arnimallee 14, 14195 Berlin, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Boreham
authors.affiliation: Institute of Experimental Physics, Freie Universität Berlin, Arnimallee 14, 14195 Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Alexiev
authors.affiliation: Institute for Pharmacy, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany. Electronic address: monika.schaefer-korting@fu-berlin.de.
authors.forename: Monika
authors.initials: M
authors.lastname: Schäfer-Korting
mesh_terms: D002110:Caffeine / Q000008:administration & dosage; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004337:Drug Carriers / Q000008:administration & dosage; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D053758:Nanoparticles / Q000008:administration & dosage; D010539:Permeability; D015595:Skin Aging / Q000187:drug effects / Q000502:physiology; D013739:Testosterone / Q000008:administration & dosage; D014466:Ultraviolet Rays; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D053582:Interleukin-1alpha; D016209:Interleukin-8; D002110:Caffeine; D013739:Testosterone; D001616:beta-Galactosidase
keywords: Drug delivery systems; Reconstructed human epidermis; Senescence-associated secretory phenotype; Skin absorption; Skin aging; Tissue engineering