title: Topical treatment with liposomes containing T4 endonuclease V protects human skin in vivo from ultraviolet-induced upregulation of interleukin-10 and tumor necrosis factor-alpha.
abstract: Exposing human skin to ultraviolet radiation causes DNA damage, sunburn, immune alterations, and eventually, skin cancer. We wished to determine whether liposomes containing a DNA repair enzyme could prevent any of the acute effects of irradiation when applied after ultraviolet exposure. Fifteen human patients with a prior history of skin cancer were exposed to two minimal erythema doses of ultraviolet radiation on their buttock skin. Liposomes containing T4 endonuclease V or heat-inactivated enzyme were applied immediately and at 2, 4, and 5 h after ultraviolet irradiation. Transmission electron microscopy after anti-T4 endonuclease V-staining and immunogold labeling on biopsies taken at 6 h after ultraviolet exposure revealed that the enzyme was present within cells in the skin. Immunohistochemical DNA damage studies suggested a trend toward improved DNA repair at the active T4 endonuclease V liposome-treated test sites. Although the active T4 endonuclease V liposomes did not significantly affect the ultraviolet-induced erythema response and microscopic sunburn cell formation, they nearly completely prevented ultraviolet-induced upregulation of interleukin-10 and tumor necrosis factor-alpha RNA message and of interleukin-10 protein. These studies demonstrate that liposomes can be used for topical intracellular delivery of small proteins to human skin and suggest that liposomes containing DNA repair enzymes may provide a new avenue for photoprotection against some forms of ultraviolet-induced skin damage.
authors.affiliation: Department of Dermatology, Karl Franzens University, Graz, Austria. peter.wolf@kfunigraz.ac.at
authors.forename: P
authors.initials: P
authors.lastname: Wolf
authors.forename: H
authors.initials: H
authors.lastname: Maier
authors.forename: R R
authors.initials: RR
authors.lastname: Müllegger
authors.forename: C A
authors.initials: CA
authors.lastname: Chadwick
authors.forename: R
authors.initials: R
authors.lastname: Hofmann-Wellenhof
authors.forename: H P
authors.initials: HP
authors.lastname: Soyer
authors.forename: A
authors.initials: A
authors.lastname: Hofer
authors.forename: J
authors.initials: J
authors.lastname: Smolle
authors.forename: M
authors.initials: M
authors.lastname: Horn
authors.forename: L
authors.initials: L
authors.lastname: Cerroni
authors.forename: D
authors.initials: D
authors.lastname: Yarosh
authors.forename: J
authors.initials: J
authors.lastname: Klein
authors.forename: C
authors.initials: C
authors.lastname: Bucana
authors.forename: K
authors.initials: K
authors.lastname: Dunner
authors.forename: C S
authors.initials: CS
authors.lastname: Potten
authors.forename: H
authors.initials: H
authors.lastname: Hönigsmann
authors.forename: H
authors.initials: H
authors.lastname: Kerl
authors.forename: M L
authors.initials: ML
authors.lastname: Kripke
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D011088:DNA Ligases / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004260:DNA Repair / Q000187:drug effects; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004337:Drug Carriers; D004706:Endodeoxyribonucleases / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D015603:Keratinocytes / Q000201:enzymology; D007801:Langerhans Cells / Q000201:enzymology; D008081:Liposomes; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D011837:Radiation-Protective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D012867:Skin / Q000187:drug effects* / Q000378:metabolism* / Q000528:radiation effects / Q000648:ultrastructure; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000187:drug effects; D014764:Viral Proteins
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D011837:Radiation-Protective Agents; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; D016753:Interleukin-10; D004706:Endodeoxyribonucleases; C470698:endonuclease V, phage T4; D043224:Deoxyribonuclease (Pyrimidine Dimer); D011088:DNA Ligases