Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06510, USA.
Am J Reprod Immunol. 2012 Sep;68(3):233-7. doi: 10.1111/j.1600-0897.2012.01164.x. Epub 2012 Jun 4.
Uterine innate immunity remains poorly characterized, and while endometrial endothelial cells are known to express Toll-like receptors (TLRs), little is known about their function in these cells. The present study evaluated the effect of Gram-negative bacterial lipopolysaccharide (LPS) on human endometrial endothelial cell (HEECs) cytokine secretion and tissue factor expression, and the role of TLR-4 in these responses.
Human endometrial endothelial cells were treated with or without LPS ± LPS-RS, a TLR-4 antagonist, via the binding of MD-2. After 24 hr, cell-free supernatants were evaluated for cytokines by multiplex analysis and cell lysates were analyzed for tissue factor expression by Western blot.
Treatment of HEECs with LPS significantly upregulated the secretion of IL-6, IL-8, and G-CSF, and this was prevented by LPS-RS. LPS also induced tissue factor expression by the HEECs; however, this was unaffected by LPS-RS.
These findings suggest that TLR-4 is functional in HEECs and its activation by bacterial LPS induces a specific cytokine/chemokine response. However, bacterial LPS also induced tissue factor expression in what seemed to be a TLR-4-independent fashion, suggesting that this bacterial component can act on the HEECs through TLR-4-dependent and TLR-4-independent pathways. These findings indicate that endometrial endothelial cells may play an active role in uterine innate immunity.
子宫内膜固有免疫仍未得到充分描述，尽管已知子宫内膜内皮细胞表达 Toll 样受体（TLR），但这些细胞中的功能知之甚少。本研究评估了革兰氏阴性细菌脂多糖（LPS）对人子宫内膜内皮细胞（HEEC）细胞因子分泌和组织因子表达的影响，以及 TLR-4 在这些反应中的作用。
通过与 MD-2 结合，用或不用 LPS±LPS-RS（TLR-4 拮抗剂）处理人子宫内膜内皮细胞。24 小时后，通过多重分析评估细胞无细胞上清液中的细胞因子，并用 Western blot 分析细胞裂解物中的组织因子表达。
LPS 处理 HEECs 可显著上调 IL-6、IL-8 和 G-CSF 的分泌，而 LPS-RS 可预防这种情况。LPS 还诱导 HEECs 表达组织因子；然而，LPS-RS 对此没有影响。
这些发现表明 TLR-4 在 HEECs 中具有功能，其被细菌 LPS 激活可诱导特定的细胞因子/趋化因子反应。然而，细菌 LPS 还以似乎不依赖 TLR-4 的方式诱导组织因子表达，表明这种细菌成分可以通过 TLR-4 依赖和 TLR-4 非依赖途径作用于 HEECs。这些发现表明子宫内膜内皮细胞可能在子宫固有免疫中发挥积极作用。
