UVB-induced alterations in permeability barrier function: roles for epidermal hyperproliferation and thymocyte-mediated response.
UV irradiation induces a variety of cutaneous responses, including disruption of epidermal permeability barrier function, the basis for which is not known. Herein, we investigated the separate roles of hyperproliferation and inflammation in the pathogenesis of UVB-induced barrier disruption. Adult hairless mice were exposed to increasing doses of UVB (1.5-7.5 MED), and transepidermal water loss (TEWL) was monitored daily for up to 7 d. The extent of TEWL increase was dependent on the UVB dose, but with all doses, the increase began after > or =48 h and peaked at 96 h, decreasing by 120 h. Epidermal [(3)H]thymidine incorporation increased at 24 h and peaked at 48 h (570%), preceding the maximal increase in TEWL. Cyclosporin A, methotrexate, 5-fluorouracil, or arabinosylcytosine significantly diminished the UVB-induced TEWL increase. Athymic nude mice also displayed a markedly diminished response to UVB, and DNA synthesis did not increased at 48 h. Transplantation of athymic mice with T-cell-enriched mixed immune cells significantly restored sensitivity to both the UVB-induced hyperproliferation and the barrier defect. Finally, although UVB exposure increased PGE2 levels in whole skin samples (2- to 3-fold within 1-3 h; p < 0.005), this increase was completely blocked by topical indomethacin, and neither topical indomethacin nor topical glucocorticoids blocked development of the barrier abnormality. These results show that (i) UVB produces delayed alteration in barrier function and (ii) both an epidermal proliferative response and thymocyte-mediated events (but not PGE2 production and nonspecific inflammation) appear to contribute to UVB-induced abrogation of the permeability barrier.
Haratake
A
A
Cosmetics Laboratory, Kanebo Limited, Odawara-shi, Kanagawa, Japan.
Uchida
Y
Y
Schmuth
M
M
Tanno
O
O
Yasuda
R
R
Epstein
J H
JH
Elias
P M
PM
Holleran
W M
WM
D000305:Adrenal Cortex Hormones / Q000502:physiology; D000818:Animals; D002455:Cell Division; D002463:Cell Membrane Permeability / Q000502:physiology* / Q000528:radiation effects*; D004247:DNA / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D004307:Dose-Response Relationship, Radiation; D006965:Hyperplasia; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012867:Skin / Q000473:pathology / Q000528:radiation effects; D013950:Thymus Gland / Q000166:cytology; D014466:Ultraviolet Rays
D000305:Adrenal Cortex Hormones; D004247:DNA; D015232:Dinoprostone