Thromboxane (TX) A₂ has been identified as an important intrahepatic vasoconstrictor upon Kupffer cell (KC) activation during infections such as spontaneous bacterial peritonitis (SBP). The study aimed to investigate the role of TLRs in the TXA₂ increase in liver nonparenchymal cells and their related mechanisms. Here, we identified TLR‐2 as a common pathway for different microbials: microbial lysates including Gram‐positive bacteria, Gram‐negative bacteria, and fungi all increased TXA₂ secretion via activation of TLR‐2 in human KCs, accompanied by increased expression and phosphorylation of Myd88‐related pathway. Of all TLR agonists, only TLR‐1, ‐2, and ‐4 agonists increased TXA₂ in human KCs. These results were further confirmed by mouse liver nonparenchymal cells. Comparing the effects of TLR‐1, ‐2, and ‐4 antagonists, only TLR‐2 antagonist showed inhibitory effects with all tested microbial lysates. Pretreatment with TLR‐2 antagonist in human KCs blocked the secretion of IL‐10, CXCL‐10, TNF‐α, and IL‐6 induced by Gram‐positive and Gram‐negative bacterial stimulation. IL‐23 and IL‐1β were only induced by Gram‐negative bacteria. Thus, TLR‐2 might be a potential marker and an attractive target for future treatment of patients with SBP. In addition, IL‐23 and IL‐1β might distinguish early between Gram‐positive and Gram‐negative SBP.

中文翻译：

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不同微生物裂解物对库普弗细胞的激活作用：Toll样受体2在小鼠和人类中血栓烷A2的产生中起关键作用。

在感染（例如自发性细菌性腹膜炎（SBP））期间，库普弗细胞（KC）激活后，血栓烷（TX）A ₂被确定为重要的肝内血管收缩剂。这项研究旨在调查TLRs在肝实质细胞中TXA ₂增加中的作用及其相关机制。在这里，我们确定了TLR-2是不同微生物的共同途径：包括革兰氏阳性菌，革兰氏阴性菌和真菌在内的微生物裂解物都通过激活人KCs中的TLR-2来增加TXA _2的分泌，并伴随着表达和表达的增加。 Myd88相关途径的磷酸化。在所有TLR激动剂中，只有TLR-1，‐2和‐4激动剂增加了TXA ₂在人类KC中。小鼠肝脏非实质细胞进一步证实了这些结果。比较TLR-1，-2和-4拮抗剂的作用，只有TLR-2拮抗剂对所有测试的微生物裂解物均显示出抑制作用。在人KC中用TLR-2拮抗剂预处理可阻止革兰氏阳性和革兰氏阴性细菌刺激诱导的IL-10，CXCL-10，TNF-α和IL-6的分泌。IL-23和IL-1β仅由革兰氏阴性细菌诱导。因此，TLR-2可能是SBP患者未来治疗的潜在标志物和有吸引力的靶标。此外，IL-23和IL-1β可能会在早期区分革兰氏阳性和阴性SBP。