Toll-like receptor 4 and MYD88-dependent signaling mechanisms of the innate immune system are essential for the response to lipopolysaccharide by epithelial and stromal cells of the bovine endometrium.
Toll-like receptor 4 and MYD88-dependent signaling mechanisms of the innate immune system are essential for the response to lipopolysaccharide by epithelial and stromal cells of the bovine endometrium.
复制标题
DOI：
10.1095/biolreprod.111.092718
复制
发表时间：
2012-02
影响因子：
3.6
通讯作者：
Sheldon IM
中科院分区：
文献类型：
--
作者：
Cronin JG;Turner ML;Goetze L;Bryant CE;Sheldon IM
革兰氏阴性菌感染牛子宫内膜通常会引起子宫疾病。免疫系统细胞上的 Toll 样受体 4 (TLR4) 与革兰氏阴性细菌脂多糖 (LPS) 结合，刺激促炎细胞因子白细胞介素 (IL)-1β 和 IL-6 以及趋化因子 IL-8 的分泌。由于子宫内膜是子宫感染的第一道屏障，因此在子宫内膜上皮和基质细胞中研究了 LPS 触发的信号级联反应以及随后炎症介质的表达，并使用短干扰 RNA (siRNA) 和生化抑制剂确定了关键途径。用超纯 LPS 处理子宫内膜细胞会刺激炎症反应，其特征是上皮细胞中 IL1B、IL6 和 IL8 mRNA 表达增加以及 IL-6 蛋白积累；并增加基质细胞中 IL1B 和 IL8 mRNA 的表达以及 IL-6 和 IL-8 蛋白的积累。用 LPS 处理子宫内膜细胞还诱导 IκB 降解和 NF-κB 核转位，以及 MAPK3/1 和 MAPK14 的快速磷酸化。使用 siRNA 敲除 TLR4 或其信号转接分子 MYD88，可减少上皮细胞和基质细胞对 LPS 的炎症反应。生化抑制 MAPK3/1（而非 JNK 或 MAPK14）可减少 LPS 诱导的子宫内膜细胞中 IL1B、IL6 和 IL8 的表达。总之，上皮细胞和基质细胞在子宫内膜的先天免疫监视中具有内在作用，对于 LPS，这种识别是通过 TLR4 和 MyD88 依赖性细胞信号传导途径发生的。
Infection of the bovine endometrium with Gram-negative bacteria commonly causes uterine disease. Toll-like receptor 4 (TLR4) on cells of the immune system bind Gram-negative bacterial lipopolysaccharide (LPS), stimulating the secretion of the pro-inflammatory cytokines interleukin (IL)-1β and IL-6, and the chemokine IL-8. As the endometrium is the first barrier to infection of the uterus, the signaling cascade triggered by LPS and the subsequent expression of inflammatory mediators was investigated in endometrial epithelial and stromal cells, and the key pathways identified using short interfering RNA (siRNA) and biochemical inhibitors. Treatment of endometrial cells with ultrapure LPS stimulated an inflammatory response characterized by increased IL1B, IL6 and IL8 mRNA expression, and IL-6 protein accumulation in epithelial cells; and increased IL1B and IL8 mRNA expression, and IL-6 and IL-8 protein accumulation in stromal cells. Treatment of endometrial cells with LPS also induced the degradation of IκB and the nuclear translocation of NF-κB, as well as rapid phosphorylation of MAPK3/1 and MAPK14. Knockdown of TLR4 or its signaling adaptor molecule, MYD88, using siRNA reduced the inflammatory response to LPS in epithelial and stromal cells. Biochemical inhibition of MAPK3/1, but not JNK, or MAPK14, reduced LPS-induced IL1B, IL6 and IL8 expression in endometrial cells. In conclusion, epithelial and stromal cells have an intrinsic role in innate immune surveillance in the endometrium, and in the case of LPS this recognition occurs via TLR4 and MyD88 dependent cell signaling pathways.
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
DOI：
10.1073/pnas.92.17.7686
发表时间：
1995-08-15
影响因子：
11.1
作者：
DUDLEY, DT;PANG, L;SALTIEL, AR
通讯作者：
SALTIEL, AR
影响因子：
56.9
作者：
HAN, J;LEE, JD;ULEVITCH, RJ
通讯作者：
ULEVITCH, RJ
影响因子：
64.8
作者：
Park, Beom Seok;Song, Dong Hyun;Lee, Jie-Oh
通讯作者：
Lee, Jie-Oh
影响因子：
5.8
作者：
Hirata, T;Osuga, Y;Taketani, Y
通讯作者：
Taketani, Y