Saed Ghassan M, Jiang Zhongliang, Fletcher Nicole M, Diamond Michael P
Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, CS Mott Center for Human Growth and Development, Wayne State University, Detroit, Michigan 48201, USA.
Fertil Steril. 2008 Nov;90(5):1925-30. doi: 10.1016/j.fertnstert.2007.06.091. Epub 2007 Oct 1.
To examine the effect of interferon (IFN)-gamma treatment under normal and hypoxic conditions on the BCL-2/BAX ratio of fibroblasts obtained from normal peritoneal and adhesion tissues of the same patients.
Prospective experimental study.
University medical center.
PATIENT(S): Fibroblasts from peritoneum and adhesion tissues of 5 patients.
INTERVENTION(S): Hypoxia and IFN-gamma treatments of fibroblasts.
MAIN OUTCOME MEASURE(S): We used the multiplex polymerase chain reaction technique to measure expression of BCL-2 and BAX in normal peritoneal and adhesion fibroblasts exposed to hypoxia (2% O(2)), in the presence or absence of IFN-gamma for different time points and dosages.
RESULT(S): At baseline, adhesion fibroblasts manifested decreased basal levels of apoptosis compared with normal fibroblasts. Hypoxia treatment resulted in a time-response decrease in apoptosis in both cell lines. Interferon-gamma treatment resulted in a dose-response increase in apoptosis in both cell lines. Hypoxia had a reduced or no effect on apoptosis in the presence of increasing doses of IFN-gamma in both cell types.
CONCLUSION(S): Interferon-gamma can block the effects of hypoxia on apoptosis, supporting the antifibrogenic nature of this cytokine. This suggests that IFN-gamma would be a good candidate for consideration for intervention in the development of peritoneal adhesions and fibrosis.
研究在正常和缺氧条件下,干扰素(IFN)-γ治疗对取自同一患者正常腹膜组织和粘连组织的成纤维细胞中BCL-2/BAX比值的影响。
前瞻性实验研究。
大学医学中心。
5例患者腹膜和粘连组织的成纤维细胞。
对成纤维细胞进行缺氧和IFN-γ处理。
我们采用多重聚合酶链反应技术,测量在不同时间点和剂量条件下,正常腹膜和粘连成纤维细胞在缺氧(2% O₂)环境中,无论有无IFN-γ时BCL-2和BAX的表达情况。
在基线时,与正常成纤维细胞相比,粘连成纤维细胞的基础凋亡水平降低。缺氧处理导致两种细胞系的凋亡随时间呈下降趋势。IFN-γ处理导致两种细胞系的凋亡随剂量增加。在两种细胞类型中,随着IFN-γ剂量增加,缺氧对凋亡的影响减弱或消失。
IFN-γ可阻断缺氧对凋亡的影响,支持这种细胞因子的抗纤维化特性。这表明IFN-γ可能是干预腹膜粘连和纤维化发展的一个很好的候选药物。