INSERM, U1016, Département Génétique et Développement, Institut Cochin, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Université Paris Descartes, Paris, France.
J Immunol. 2011 Sep 1;187(5):2766-74. doi: 10.4049/jimmunol.1100217. Epub 2011 Jul 20.
Intrauterine infection is a major cause of spontaneous preterm birth. Amniotic epithelial cells represent the first line of defense against intra-amniotic bacteria. We hypothesize that this epithelial cell barrier is able to recognize and respond to pathogens through the function of TLRs, which are crucial regulators of the innate immune system. In this study, we describe the expression of transcripts for TLR1-TLR10 in human amniotic epithelial cells. We show that amniotic epithelial cells express functional TLR5, TLR6/2, and TLR4. Activation by TLR5 and TLR6/2 agonists produces IL-6 and IL-8, concomitantly with the activation of NF-κB signaling pathway, matrix metalloproteinase-9 induction, and PTGS2 expression. In contrast, TLR4 activation reduced amniotic epithelial cell viability and induced cell apoptosis evidenced by an elevated Bax/Bcl-2 ratio and cleavage of caspase-3. These data suggest specific TLR-mediated functions in human amniotic epithelial cells for initiating different immune responses, which ultimately may lead to preterm birth.
宫内感染是自发性早产的主要原因。羊膜上皮细胞是防止羊膜内细菌感染的第一道防线。我们假设，这种上皮细胞屏障能够通过 TLR 的功能来识别和应对病原体，TLR 是先天免疫系统的关键调节因子。在这项研究中，我们描述了人羊膜上皮细胞中 TLR1-TLR10 转录本的表达。我们发现羊膜上皮细胞表达功能性 TLR5、TLR6/2 和 TLR4。TLR5 和 TLR6/2 激动剂的激活会产生 IL-6 和 IL-8，同时激活 NF-κB 信号通路、诱导基质金属蛋白酶-9 的表达和 PTGS2。相比之下，TLR4 的激活降低了羊膜上皮细胞的活力，并诱导细胞凋亡，证据是 Bax/Bcl-2 比值升高和 caspase-3 的裂解。这些数据表明，人羊膜上皮细胞中特定的 TLR 介导功能可引发不同的免疫反应，最终可能导致早产。
