Tanaka Tetsuji, Umesaki Naohiko
Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama 641-0012, Japan.
Int J Mol Med. 2003 Jun;11(6):757-62.
Fas antigen (CD95) is expressed on almost all types of human cells and is believed to mediate receptor-specific apoptotic signals. In human endometrial tissues, high Fas and Fas ligand expressions and Fas-mediated apoptosis in endometrial epithelial cells have been discussed in many reports but no study has examined Fas-mediated signals in endometrial stromal cells. In this study we investigated Fas expression and Fas-mediated signals of normal human endometrial stromal cells. Flow cytometric analysis revealed Fas antigen expression on the stromal cells and their Fas expression was enhanced by 8-Br-cAMP, a strong inducer of decidualization. Neither short-term nor long-term cultures with anti-Fas IgM affected proliferation or viability of the stromal cells. Anti-Fas IgM alone affected neither viable cell numbers nor PRL release of unstimulated stromal cells. However, anti-Fas IgM dose-dependently stimulated viable cell numbers of stromal cells co-stimulated with 8-Br-cAMP and anti-Fas IgM, whereas PRL secretion of the co-stimulated cells was not affected. Anti-Fas IgM dose-dependently stimulated viable cell numbers of 8-Br-cAMP-stimulated cells but did not affect PRL secretion of 8-Br-cAMP-induced decidualized cells. These results indicate that Fas antigen on human endometrial stromal cells cannot mediate receptor-specific apoptotic signals, and that Fas-mediated signals stimulate survival of 8-Br-cAMP-stimulated non-decidualized stromal cells. Thus, stimulation of Fas-antigen on the endometrial stromal cells enhances anti-apoptotic/survival signals in certain stromal cells, autoregulating functional cellular subpopulations of human endometrial stromal cells in a paracrine manner.
Fas抗原（CD95）在几乎所有类型的人类细胞上均有表达，据信其介导受体特异性凋亡信号。在人类子宫内膜组织中，许多报告都讨论了子宫内膜上皮细胞中Fas和Fas配体的高表达以及Fas介导的凋亡，但尚无研究检测子宫内膜基质细胞中Fas介导的信号。在本研究中，我们调查了正常人类子宫内膜基质细胞的Fas表达和Fas介导的信号。流式细胞术分析显示基质细胞上有Fas抗原表达，并且其Fas表达可被8 - Br - cAMP（一种强力的蜕膜化诱导剂）增强。用抗Fas IgM进行短期或长期培养均未影响基质细胞的增殖或活力。单独的抗Fas IgM既不影响未刺激的基质细胞的活细胞数量，也不影响其催乳素释放。然而，抗Fas IgM剂量依赖性地刺激了与8 - Br - cAMP和抗Fas IgM共同刺激的基质细胞的活细胞数量，而共同刺激细胞的催乳素分泌未受影响。抗Fas IgM剂量依赖性地刺激了8 - Br - cAMP刺激的细胞的活细胞数量，但不影响8 - Br - cAMP诱导的蜕膜化细胞的催乳素分泌。这些结果表明，人类子宫内膜基质细胞上的Fas抗原不能介导受体特异性凋亡信号，并且Fas介导的信号刺激了8 - Br - cAMP刺激的未蜕膜化基质细胞的存活。因此，刺激子宫内膜基质细胞上的Fas抗原可增强某些基质细胞中的抗凋亡/存活信号，以旁分泌方式自动调节人类子宫内膜基质细胞的功能性细胞亚群。
