Toll-like receptor 4 mediates the response of epithelial and stromal cells to lipopolysaccharide in the endometrium.
Toll-like receptor 4 mediates the response of epithelial and stromal cells to lipopolysaccharide in the endometrium.
复制标题
DOI：
10.1371/journal.pone.0012906
复制
发表时间：
2010-09-22
期刊：
影响因子：
3.7
通讯作者：
Roberts MH
中科院分区：
文献类型：
--
作者：
Sheldon IM;Roberts MH
女性生殖道细菌上行感染导致盆腔炎（PID）、早产和不孕。脂多糖（LPS）是革兰氏阴性菌细胞壁的主要成分。天然免疫依赖于宿主细胞上Toll样受体4（TLR 4）对LPS的检测。LPS与免疫细胞上的TLR 4的结合刺激促炎细胞因子如IL-6、趋化因子如CXCL 1和CCL 20以及前列腺素E2的分泌。本研究验证了子宫内膜上皮细胞和间质细胞上的TLR 4对于女性生殖道对LPS的先天性免疫应答是必不可少的这一假设。野生型（WT）小鼠在子宫内膜中表达TLR 4。子宫内输注纯化的LPS导致盆腔炎，WT小鼠子宫内膜中粒细胞聚集，但Tlr 4 −/−小鼠没有。腹腔内输注LPS在WT或Tlr 4 −/−小鼠中没有引起PID，表明子宫内膜中的TLR 4对于检测雌性生殖道中的LPS的重要性。从WT而不是Tlr 4 −/−小鼠的子宫内膜分离的基质和上皮细胞以浓度和时间依赖性方式分泌IL-6、CXCL 1、CCL 20和前列腺素E2以响应LPS。来自WT和Tlr 4 −/−小鼠的基质和上皮细胞的组合的共培养提供了对LPS的反应中基质-上皮相互作用的很少证据。女性生殖道内对LPS的先天性免疫应答依赖于子宫内膜上皮细胞和基质细胞上的TLR 4。
Ascending infections of the female genital tract with bacteria causes pelvic inflammatory disease (PID), preterm labour and infertility. Lipopolysaccharide (LPS) is the main component of the cell wall of Gram-negative bacteria. Innate immunity relies on the detection of LPS by Toll-like receptor 4 (TLR4) on host cells. Binding of LPS to TLR4 on immune cells stimulates secretion of pro-inflammatory cytokines such as IL-6, chemokines such as CXCL1 and CCL20, and prostaglandin E2. The present study tested the hypothesis that TLR4 on endometrial epithelial and stromal cells is essential for the innate immune response to LPS in the female genital tract. Wild type (WT) mice expressed TLR4 in the endometrium. Intrauterine infusion of purified LPS caused pelvic inflammatory disease, with accumulation of granulocytes throughout the endometrium of WT but not Tlr4−/− mice. Intra-peritoneal infusion of LPS did not cause PID in WT or Tlr4−/− mice, indicating the importance of TLR4 in the endometrium for the detection of LPS in the female genital tract. Stromal and epithelial cells isolated from the endometrium of WT but not Tlr4−/− mice, secreted IL-6, CXCL1, CCL20 and prostaglandin E2 in response to LPS, in a concentration and time dependent manner. Co-culture of combinations of stromal and epithelial cells from WT and Tlr4−/− mice provided little evidence of stromal-epithelial interactions in the response to LPS. The innate immune response to LPS in the female genital tract is dependent on TLR4 on the epithelial and stromal cells of the endometrium.
登录
查看更多内容
DOI：
10.1186/1477-7827-7-55
发表时间：
2009-05-29
期刊：
Reproductive biology and endocrinology : RB&E
影响因子：
--
作者：
Herath S;Lilly ST;Santos NR;Gilbert RO;Goetze L;Bryant CE;White JO;Cronin J;Sheldon IM
通讯作者：
Sheldon IM
影响因子：
56.9
作者：
Ernst, RK;Yi, EC;Miller, SI
通讯作者：
Miller, SI
影响因子：
6.1
作者：
Aflatoonian, R.;Tuckerman, E.;Fazeli, A.
通讯作者：
Fazeli, A.
影响因子：
6.1
作者：
Fazeli, A;Bruce, C;Anumba, DO
通讯作者：
Anumba, DO
影响因子：
5.5
作者：
Beutler, B;Hoebe, K;Ulevitch, RJ
通讯作者：
Ulevitch, RJ