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.
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.
Wolf
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P
Department of Dermatology, Karl Franzens University, Graz, Austria. peter.wolf@kfunigraz.ac.at
Maier
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H
Müllegger
R R
RR
Chadwick
C A
CA
Hofmann-Wellenhof
R
R
Soyer
H P
HP
Hofer
A
A
Smolle
J
J
Horn
M
M
Cerroni
L
L
Yarosh
D
D
Klein
J
J
Bucana
C
C
Dunner
K
K
Potten
C S
CS
Hönigsmann
H
H
Kerl
H
H
Kripke
M L
ML
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
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