引用

脂多糖(LPS)的反复刺激通过调节toll样受体4 (TLR4)改变对随后LPS暴露的反应。其他TLRs的激活是否可以调节TLR4的反应，反之亦然，目前尚不清楚。特别是对于内皮细胞(先天免疫的关键组成部分)，TLR交叉调制的影响尚不清楚。我们假设TLR2启动(通过Pam3Csk4)将抑制tlr4介导的反应，而TLR3启动(通过Poly I:C)将增强随后的tlr4炎症信号。我们研究了人脐静脉内皮细胞和新生儿皮肤微血管内皮细胞。用Poly I:C (10 g/ml)、Pam3Csk4 (10 g/ml)或LPS (100 ng/ml)组合引物细胞，然后清洗并静置。然后用Poly I:C、Pam3Csk4或LPS对它们进行再挑战。内皮细胞对LPS的反复刺激表现出明显的耐受性。尽管与人脐静脉内皮细胞相比，HMVECs对Pam3Csk4的促炎反应减弱，但Pam3Csk4启动也降低了这两种细胞类型对继发性LPS刺激的反应。Poly I:C启动分别增强了Poly I:C或LPS再挑战时产生炎症和干扰素的信号。 Poly I:C priming also induced interferon regulatory factor 7, leading to enhancement of interferon production. Finally, both Poly I:C and LPS priming induced significant changes in receptor-interacting serine/threonine-protein kinase 1 activity. Pharmacological inhibition of receptor-interacting serine/threonine-protein kinase 1 or interferon regulatory factor 7 reduced the potentiated phenotype of TLR3 priming on TLR4 rechallenge. These results demonstrate that in human endothelial cells, prior activation of TLRs can have a significant impact on subsequent exposures and may contribute to the severity of the host response.