Hiramoto Keiichi, Tanaka Hiroshi, Yanagihara Nobuyo, Sato Eisuke F, Inoue Masayasu
Department of Biochemistry and Molecular Pathology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, 545-8585, Osaka City, Osaka, Japan.
Arch Dermatol Res. 2004 Feb;295(8-9):307-11. doi: 10.1007/s00403-003-0437-0. Epub 2003 Nov 29.
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.
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.
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.
These results suggest that 17beta-estradiol prevents UVB-induced suppression of the CHS response caused by immunosuppressive cytokines produced by keratinocytes.
女性患皮肤癌的风险低于男性，紫外线（UV）辐射引起的光免疫抑制被认为与皮肤癌的进展有关。目的：确定17β-雌二醇对紫外线B（UVB）照射引起的免疫抑制和接触性超敏反应（CHS）的影响。
通过单次UVB照射（10 kJ/m2），对经皮肤用0.5%异硫氰酸荧光素（FITC）致敏的C57BL小鼠诱导全身免疫抑制。在用17β-雌二醇、他莫昔芬（17β-雌二醇拮抗剂）或抗雌二醇抗体腹腔注射处理的小鼠身上涂抹FITC后，评估CHS反应。使用酶联免疫吸附测定（ELISA）测量处理组小鼠和对照组小鼠血清白细胞介素-10（IL-10）的水平。为了评估17β-雌二醇对角质形成细胞的影响，将Pam-212细胞在体外暴露于UVB辐射并用17β-雌二醇处理24小时。使用ELISA测量上清液中的IL-10含量。
与未照射的小鼠相比，UVB照射小鼠的CHS反应受到显著抑制。连续腹腔注射17β-雌二醇可显著减轻UVB诱导的雄性小鼠CHS反应抑制，而注射他莫昔芬或抗雌二醇抗体则显著促进UVB诱导的雌性小鼠抑制。UVB照射后，用17β-雌二醇处理可降低CHS抑制的雄性小鼠血清IL-10水平，但用他莫昔芬或抗雌二醇抗体处理可增加雌性小鼠血清IL-10水平。用17β-雌二醇处理以剂量依赖性方式降低UVB照射的Pam-212细胞产生的IL-10。
这些结果表明，17β-雌二醇可预防UVB诱导的由角质形成细胞产生的免疫抑制细胞因子引起的CHS反应抑制。
