Aziz K E, Wakefield D
Immunopathology Department, Prince Henry Hospital, School of Pathology, University of New South Wales, Anzac Parade, Little Bay, New South Wales, Australia.
Cell Immunol. 1996 Jan 10;167(1):79-85. doi: 10.1006/cimm.1996.0010.
The aim of this study was to examine the effects of beta-estradiol, progesterone, and dexamethasone on cytokine-stimulated endothelial cell expression of adhesion molecules. TNF-alpha (250 U/mL) and IL-1 alpha (50 U/mL) were used to stimulate the endothelial cells for 6 or 23 hr in vitro. Indirect immunofluorescence and flow cytometry were used to quantitate expression of adhesion molecules. After 6 hr stimulation with TNF-alpha increased expression of E-selectin (P < 0.03) was noted with beta-estradiol. Strong suppression of ICAM-1 (P < 0.005) and E-selectin (P < 0.005) expression was evident with dexamethasone, which did not influence VCAM-1 expression. After 6 hr stimulation with IL-1 alpha suppression of E-selectin was observed with progesterone (P < 0.001). Dexamethasone had strong suppressive effects on ICAM-1 (P < 0.001), E-selectin (P < 0.0001), and VCAM-1 (P < 0.0002). After 23 hr stimulation with IL-1 alpha or TNF-alpha none of the examined steroids showed a significant effect on the fluorescence intensity of adhesion molecules, although there was a slight increase of the percentage of ICAM-1 positive cells with high concentrations of beta-estradiol after stimulation with TNF-alpha. Beta-estradiol and progesterone are modulatory factors of E-selectin expression on endothelial cell in vitro. Dexamethasone reduces adhesion molecule expression over endothelial cells after cytokine stimulation. These effects may be important in understanding the role of these steroids in autoimmune diseases.
本研究的目的是检测β-雌二醇、孕酮和地塞米松对细胞因子刺激的内皮细胞黏附分子表达的影响。使用肿瘤坏死因子-α(TNF-α,250 U/mL)和白细胞介素-1α(IL-1α,50 U/mL)在体外刺激内皮细胞6小时或23小时。采用间接免疫荧光和流式细胞术对黏附分子的表达进行定量。在用TNF-α刺激6小时后,β-雌二醇可使E-选择素表达增加(P < 0.03)。地塞米松可显著抑制细胞间黏附分子-1(ICAM-1,P < 0.005)和E-选择素(P < 0.005)的表达,但不影响血管细胞黏附分子-1(VCAM-1)的表达。在用IL-1α刺激6小时后,孕酮可抑制E-选择素的表达(P < 0.001)。地塞米松对ICAM-1(P < 0.001)、E-选择素(P < 0.0001)和VCAM-1(P < 0.0002)均有强烈的抑制作用。在用IL-1α或TNF-α刺激23小时后,尽管在用TNF-α刺激后高浓度β-雌二醇可使ICAM-1阳性细胞百分比略有增加,但所检测的类固醇均未对黏附分子的荧光强度产生显著影响。β-雌二醇和孕酮是体外内皮细胞E-选择素表达的调节因子。地塞米松可降低细胞因子刺激后内皮细胞黏附分子的表达。这些作用对于理解这些类固醇在自身免疫性疾病中的作用可能具有重要意义。