Ultraviolet light is one of the major environmental factors to which humans are exposed and is known to be a significant cause of human skin cancer. Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce several types of cancers in humans and rodents. NSAIDs are believed to act by inhibiting the cyclooxygenases (COX), and we have observed that both COX-1 and COX-2 deficiencies reduce mouse skin papilloma formation by about 80% in the initiation/ promotion model with the data suggesting that altered keratinocyte differentiation may be responsible. Our studies with UV indicate that mice deficient in COX-2, but not COX-1, exhibit dose dependent increases in epidermal skin damage and cell death compared to wild type mice. Levels of apoptosis were increased about 2-fold in COX-2 null mice compared to COX-1 null or wild type mice. The COX-2 null mice also recovered from the UV induced epidermal damage more slowly then did wild type mice.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES021229-03
Application #
6681902
Study Section
(LECM)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2002
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Chun, Kyung-Soo; Langenbach, Robert (2007) A proposed COX-2 and PGE(2) receptor interaction in UV-exposed mouse skin. Mol Carcinog 46:699-704
Akunda, Jacqueline K; Chun, Kyung-Soo; Sessoms, Alisha R et al. (2007) Cyclooxygenase-2 deficiency increases epidermal apoptosis and impairs recovery following acute UVB exposure. Mol Carcinog 46:354-62
Fischer, Susan M; Pavone, Amy; Mikulec, Carol et al. (2007) Cyclooxygenase-2 expression is critical for chronic UV-induced murine skin carcinogenesis. Mol Carcinog 46:363-71
Chun, Kyung-Soo; Akunda, Jacqueline K; Langenbach, Robert (2007) Cyclooxygenase-2 inhibits UVB-induced apoptosis in mouse skin by activating the prostaglandin E2 receptors, EP2 and EP4. Cancer Res 67:2015-21
Rao, Jagadeesh S; Langenbach, Robert; Bosetti, Francesca (2005) Down-regulation of brain nuclear factor-kappa B pathway in the cyclooxygenase-2 knockout mouse. Brain Res Mol Brain Res 139:217-24
Wormser, Uri; Langenbach, Robert; Peddada, Shyamal et al. (2004) Reduced sulfur mustard-induced skin toxicity in cyclooxygenase-2 knockout and celecoxib-treated mice. Toxicol Appl Pharmacol 200:40-7