UVB-INDUCED ALTERATIONS IN PERMEABILITY BARRIER FUNCTION - ROLES FOR EPIDERMAL HYPERPROLIFERATION AND THYMOCYTE-MEDIATED RESPONSE

UV irradiation induces a variety of cutaneous responses, including dis ruption of epidermal permeability barrier function, the basis for whic h is not known, Herein, we investigated the separate roles of hyperpro liferation and inflammation in the pathogenesis of UVB-induced barrier disruption, Adult hairless mice were exposed to increasing doses of U VB (1.5-7.5 MED), and transepidermal water loss (TEWL) was monitored d aily for up to 7 d, The extent of TEWL increase was dependent on the U VB dose, but with all doses, the increase began after greater than or equal to 48 h and peaked at 96 h, decreasing by 120 h, Epidermal [H-3] thymidine incorporation increased at 24 h and peaked at 48 h (570%), p receding the maximal increase in TEWL. Cyclosporin A, methotrexate, 5- fluorouracil, or arabinosylcytosine significantly diminished the UVB-i nduced TEWL increase, Athymic nude mice also displayed a markedly dimi nished response to UVB, and DNA synthesis did not increased at 48 h, T ransplantation of athymic mice with T-cell-enriched mixed immune cells significantly restored sensitivity to both the UVB-induced hyperproli feration and the barrier defect, Finally, although UVB exposure increa sed PGE, 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 d evelopment of the barrier abnormality. These results show that (i) UVB produces delayed alteration in barrier function and (ii) both an epid ermal proliferative response and thymocyte-mediated events (but not PG E(2) production and nonspecific inflammation) appear to contribute to UVB-induced abrogation of the permeability barrier.