Cyclooxygenase-2 deficiency increases epidermal apoptosis and impairs recovery following acute UVB exposure

被引:28
作者
Akunda, Jacqueline K.
Chun, Kyung-Soo
Sessoms, Alisha R.
Lao, Huei-Chen
Fischer, Susan M.
Langenbach, Robert
机构
[1] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA
[2] Univ Texas, MD Anderson Canc Ctr, Div Sci Pk Res, Smithville, TX 78957 USA
关键词
cyclooxygenase; prostaglandin; UV; apoptosis;
D O I
10.1002/mc.20290
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The cyclooxygenases, COX-1 and COX-2, are involved in cutaneous responses to both acute and chronic UV exposure. In the present study, wild-type (WT), COX-1-/- and COX-2-/- mice were used to determine the influence of the individual isoform on mouse skin responses to acute UVB treatment. Immunohistochemistry and Western analysis indicated that COX-2, and not COX-1, was induced by UVB,2.5 or 5.0 kJ/m(2)), but that COX-1 remained the major source of prostaglandin E-2 production. UVB exposure significantly increased epidermal apoptosis in all genotypes compared to untreated mice. However, while the number of apoptotic cells in WT and COX-1-/- mice were about equal, the number of apoptotic cells was 2.5-fold greater in COX-2-/- mice. Apoptosis in WT and COX-2-/- mice peaked at 24 h post-exposure. The increased apoptosis and reduced proliferation in COX-2-/- mice resulted in about a 50% decrease in epidermal thickness at 24-48 h post-exposure compared to about a 50% increase in epidermal thickness in WT mice. UVB-induced cell replication, as measured by BrdU labeling, was reduced in COX-2-/- compared to WT mice at 24-96 h. However, by 96 h post-exposure, both WT and COX-2-/- mice showed epidermal hyperplasia. The data indicate that COX-2 induction initially protects against the acute sunburn effects of UVB, but that continuous induction of COX-2 may contribute to skin cancer in chronic UVB exposure. (c) 2007 Wiley-Liss, Inc.
引用
收藏
页码:354 / 362
页数:9
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