K. Kuwamoto et al., Possible involvement of enhanced prostaglandin E-2 production in the photosensitivity in xeroderma pigmentosum group A model mice, J INVES DER, 114(2), 2000, pp. 241-246
Xeroderma pigmentosum group A (XPA) gene-deficient mice cannot repair UV-in
duced DNA damage and easily develop skin cancers by UV irradiation. Therefo
re, XPA-deficient mice are a useful model of human XP and represent a promi
sing tool for photobiologic studies of the disorder, Exposure to ultraviole
t (UV) B (280-320 nm) radiation greatly enhanced inflammation and immunosup
pression in these mice. To investigate the molecular mechanisms of enhanced
UV inflammation and immunosuppression, we determined the amount of prostag
landin (PG) E-2, an inflammatory mediator and immunomodulator, and analysed
the expression of cyclooxygenase (COX) mRNA in the ear skin of XPA-deficie
nt mice after UV irradiation. In XPA-deficient mice, the amount of PGE(2) s
ignificantly increased at 48 and 72 h after UVB irradiation to the level th
at was 8- and 16-fold higher than those in wild-type mice, respectively. Th
e expression level of COX-2 mRNA increased in a time-dependent manner, alth
ough COX-1 mRNA was constantly expressed. Treatment with indomethacin, a po
tent inhibitor of PG biosynthesis, inhibited UV-induced ear swelling, abrog
ated local immunosuppression, and decreased the amount of PGE(2) in the ear
skin of XPA-deficient mice, These results indicate that the excess DNA pho
toproducts remaining in XPA-deficient cells after UV radiation may induce C
OX-2 expression. The induced production of PGE(2) may be involved in the en
hanced inflammation and immunosuppression caused by UV radiation in XPA-def
icient mice and XP patients.