Granulosa cell subtypes respond by autophagy or cell death to oxLDL-dependent activation of the oxidized lipoprotein receptor 1 and toll-like 4 receptor
Granulosa cell subtypes respond by autophagy or cell death to oxLDL-dependent activation of the oxidized lipoprotein receptor 1 and toll-like 4 receptor
复制标题
DOI：
10.4161/auto.5.7.9507
复制
发表时间：
2009-10-01
期刊：
影响因子：
13.3
通讯作者：
Spanel-Borowski, Katharina
中科院分区：
文献类型：
--
作者：
Serke, Heike;Vilser, Constanze;Spanel-Borowski, Katharina
在颗粒细胞培养物中，通过凝集素样氧化低密度脂蛋白受体1（LOX-1）的oxLDL依赖性激活观察到自噬性细胞死亡。细胞角蛋白阳性（CK+）和CK-颗粒细胞的激活可能不同。特别是LOX-1和Toll样受体4（TLR 4），先天免疫的模式识别受体之一，可能是dilateral调节。从接受体外受精（IVF）治疗的患者的卵泡收获物中建立颗粒细胞亚型培养物。响应于oxLDL处理，成纤维细胞样CK-细胞上调LOX-1并表现出修复性自噬，其可被抗LOX-1抗体阻断。类上皮样CK+细胞不调节LOX-1的表达后，oxLDL/nDL应用，但TLR 4和CD 14的表达增加0和36小时之间的oxLDL/nDL处理。这种上调与基于不存在裂解的半胱天冬酶-3的非凋亡性细胞死亡相关。活性氧（ROS）增加与12小时oxLDL应用和类固醇生成急性调节（星星）蛋白的表达是可以忽略不计的。在CK-1细胞中，TLR 4的抑制下调LOX-1并诱导凋亡。我们的结论是，CK-颗粒细胞的保护oxLDL依赖性细胞凋亡的TLR 4，而在CK+细胞，oxLDL诱导的TLR 4激活触发非凋亡性细胞死亡。CK+细胞可能代表参与卵巢重塑过程的免疫样颗粒细胞。
Autophagic cell death has been observed in granulosa cell cultures via the oxLDL-dependent activation of lectin-like oxidized low density lipoprotein receptor 1 (LOX-1). This activation might differ for cytokeratin-positive (CK+) and CK- granulosa cells. In particular, LOX-1 and toll-like receptor 4 (TLR4), one of the pattern recognition receptors of innate immunity, might be diversely regulated. Granulosa cell subtype cultures were established from the follicle harvests of patients undergoing in vitro fertilization (IVF) therapy. In response to oxLDL treatment, the fibroblast-like CK- cells upregulated LOX-1 and exhibited reparative autophagy, which could be blocked with anti-LOX-1 antibody. The epithelioid-like CK+ cells did not regulate LOX-1 expression upon oxLDL application, but the expression of TLR4 and CD14 increased between 0 and 36 h of oxLDL/nDL treatment. This upregulation was associated with nonapoptotic cell death based on the absence of cleaved caspase-3. Reactive oxygen species (ROS) increased with 12 h oxLDL application and steroidogenic acute regulatory (StAR) protein expression was negligible. In CK- cells, the inhibition of TLR4 downregulated LOX-1 and induced apoptosis. We concluded that CK- granulosa cells are protected against oxLDL-dependent apoptosis by TLR4, whereas, in CK+ cells, oxLDL-induced TLR4 activation triggers nonapoptotic cell death. The CK+ cells might represent immune-like granulosa cells involved in ovarian remodeling processes.