当前位置: X-MOL 学术Dev. Comp. Immunol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Prostaglandin I2 (PGI2) inhibits Brucella abortus internalization in macrophages via PGI2 receptor signaling, and its analogue affects immune response and disease outcome in mice
Developmental & Comparative Immunology ( IF 2.7 ) Pub Date : 2020-10-19 , DOI: 10.1016/j.dci.2020.103902
Son Hai Vu 1 , Alisha Wehdnesday Bernardo Reyes 2 , Tran Xuan Ngoc Huy 2 , Wongi Min 2 , Hu Jang Lee 2 , Hyun-Jin Kim 2 , John Hwa Lee 3 , Suk Kim 2
Affiliation  

To date, the implications of prostaglandin I2 (PGI2), a prominent lipid mediator for modulation of immune responses, has not been clearly understood in Brucella infection. In this study, we found that cyclooxygenase-2 (COX-2) was significantly expressed in both infected bone marrow-derived macrophages (BMMs) and RAW 264.7 cells. Prostaglandin I2 synthase (PTGIS) expression was not significantly changed, and PGI2 receptor (PTGIR) expression was downregulated in BMMs but upregulated in RAW 264.7 macrophages at late infection. Here, we presented that PGI2, a COX-derived metabolite, was produced by macrophages during Brucella infection and its production was regulated by COX-2 and IL-10. We suggested that PGI2 and selexipag, a potent PGI2 analogue, inhibited Brucella internalization through IP signaling which led to down-regulation of F-actin polymerization and p38α MAPK activity. Administration with selexipag suppressed immune responses and resulted in a notable reduction in bacterial burden in spleen of Brucella-challenged mice. Taken together, our study is the first to characterize PGI2 synthesis and its effect in evasion strategy of macrophages against Brucella infection.



中文翻译:

前列腺素 I2 (PGI2) 通过 PGI2 受体信号传导抑制流产布鲁氏菌在巨噬细胞中的内化,其类似物影响小鼠的免疫反应和疾病结果

迄今为止,前列腺素 I2 (PGI 2 ) 是一种用于调节免疫反应的重要脂质介质,其在布鲁氏菌感染中的作用尚未明确。在这项研究中,我们发现cyclooxygenase-2 ( COX-2 ) 在受感染的骨髓衍生巨噬细胞 (BMM) 和 RAW 264.7 细胞中均显着表达。前列腺素 I2 合酶( PTGIS ) 表达没有显着变化,PGI 2 受体( PTGIR ) 表达在 BMM 中下调,但在感染晚期 RAW 264.7 巨噬细胞中上调。在这里,我们介绍了 PGI 2是一种 COX 衍生代谢物,在布鲁氏菌感染期间由巨噬细胞产生,其产生受 COX-2 和 IL-10 的调节。我们建议 PGI 2和 selexipag(一种有效的 PGI 2类似物)通过 IP 信号传导抑制布鲁氏菌内化,从而导致 F-肌动蛋白聚合和 p38α MAPK 活性的下调。服用司来帕格可抑制免疫反应,并导致布鲁氏菌攻击小鼠脾脏中的细菌负荷显着降低。总之,我们的研究首次描述了 PGI 2合成及其在巨噬细胞对布鲁氏菌感染的逃避策略中的作用。

更新日期:2020-10-30
down
wechat
bug