Effect of 17beta-estradiol on immunosuppression induced by ultraviolet B irradiation.
BACKGROUND
The risk of skin cancer is lower in females than in males, and photoimmunosuppression caused by ultraviolet (UV) radiation is thought to be involved in the progression of skin cancer. OBJECTIVES. To determine the effect of 17beta-estradiol on immunosuppression and contact hypersensitivity (CHS) caused by ultraviolet B (UVB) irradiation.


METHODS
Systemic immunosuppression was induced in C57BL mice that had been sensitized with 0.5% fluorescein isothiocyanate (FITC) through the skin by a single exposure to UVB (10 kJ/m2). The CHS response was assessed after applying FITC to mice treated intraperitoneally with 17beta-estradiol, tamoxifen (17beta-estradiol antagonist), or antiestradiol antibody. Levels of serum interleukin-10 (IL-10) were measured in treated mice and control mice using an enzyme-linked immunosorbent assay (ELISA). To assess the effect of 17beta-estradiol on keratinocytes, Pam-212 cells were exposed in vitro to UVB radiation and treated for 24 h with 17beta-estradiol. The IL-10 content of the supernatant was measured using an ELISA.


RESULTS
The CHS response in UVB-irradiated mice was significantly suppressed in comparison to that in nonirradiated mice. Consecutive intraperitoneal injections of 17beta-estradiol significantly reduced UVB-induced suppression of the CHS response in male mice, whereas injection of tamoxifen or antiestradiol antibody significantly promoted UVB-induced suppression in female mice. Treatment with 17beta-estradiol decreased the serum IL-10 levels in CHS-suppressed male mice after UVB irradiation, but treatment with tamoxifen or antiestradiol antibody increased the serum IL-10 levels in female mice. Treatment with 17beta-estradiol reduced IL-10 production by UVB-irradiated Pam-212 cells in a dose-dependent manner.


CONCLUSIONS
These results suggest that 17beta-estradiol prevents UVB-induced suppression of the CHS response caused by immunosuppressive cytokines produced by keratinocytes.
Hiramoto
Keiichi
K
Department of Biochemistry and Molecular Pathology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, 545-8585, Osaka City, Osaka, Japan. hiramoto@msic.med.osaka-cu.ac.jp
Tanaka
Hiroshi
H
Yanagihara
Nobuyo
N
Sato
Eisuke F
EF
Inoue
Masayasu
M
D000818:Animals; D003877:Dermatitis, Contact / Q000276:immunology; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000494:pharmacology; D007108:Immune Tolerance / Q000187:drug effects* / Q000528:radiation effects*; D016753:Interleukin-10 / Q000378:metabolism; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012867:Skin / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D013047:Specific Pathogen-Free Organisms; D013629:Tamoxifen / Q000494:pharmacology; D014466:Ultraviolet Rays
D004965:Estrogen Antagonists; D005456:Fluorescent Dyes; D013629:Tamoxifen; D016753:Interleukin-10; D004958:Estradiol; D016650:Fluorescein-5-isothiocyanate