Premium
Cyclooxygenase‐2 deficiency increases epidermal apoptosis and impairs recovery following acute UVB exposure
Author(s) -
Akunda Jacqueline K.,
Chun KyungSoo,
Sessoms Alisha R.,
Lao HueiChen,
Fischer Susan M.,
Langenbach Robert
Publication year - 2007
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20290
Subject(s) - apoptosis , biology , prostaglandin e2 , cyclooxygenase , ratón , microbiology and biotechnology , endocrinology , andrology , enzyme , medicine , biochemistry
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. © 2007 Wiley‐Liss, Inc.