Notch Signaling Ligand Jagged1 Enhances Macrophage-Mediated Response to Helicobacter pylori.
Notch Signaling Ligand Jagged1 Enhances Macrophage-Mediated Response to Helicobacter pylori.
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DOI：
10.3389/fmicb.2021.692832
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发表时间：
2021
影响因子：
5.2
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Wen J;Chen C;Luo M;Liu X;Guo J;Wei T;Gu X;Gu S;Ning Y;Li Y
幽门螺杆菌（H.幽门螺杆菌）是主要定植于胃粘膜并引起许多胃肠道疾病如胃炎、消化性溃疡和胃癌的革兰氏阴性细菌之一。巨噬细胞在根除H.幽门。最近的研究表明，Notch信号可以调节巨噬细胞的活化和杀菌活性。Notch信号在巨噬细胞抗H. pylori仍不清楚。在本研究中，在巨噬细胞与H。pylori感染后，γ-分泌酶抑制Notch信号通路可降低诱导型一氧化氮合酶（iNOS）及其产物一氧化氮（NO）的表达，下调促炎细胞因子的分泌，减弱巨噬细胞对H.幽门。此外，我们发现Notch信号配体Jagged 1在H.幽门。临床标本显示，H.幽门螺杆菌感染组显著高于健康对照组。Jagged 1的过表达可促进巨噬细胞对H. pylori和siRNA-Jagged 1则表现出相反的作用。此外，外源性rJagged 1的加入促进了巨噬细胞对H.这些结果提示Jagged 1是巨噬细胞抗幽门螺杆菌的促进分子。pylori的表达，为探索Jagged 1作为控制H.幽门感染
Helicobacter pylori (H. pylori) is one of the gram-negative bacteria that mainly colonize the stomach mucosa and cause many gastrointestinal diseases, such as gastritis, peptic ulcer, and gastric cancer. Macrophages play a key role in eradicating H. pylori. Recent data have shown that Notch signaling could modulate the activation and bactericidal activities of macrophages. However, the role of Notch signaling in macrophages against H. pylori remains unclear. In the present study, in the co-culture model of macrophages with H. pylori, the inhibition of Notch signaling using γ-secretase decreased the expression of inducible nitric oxide synthase (iNOS) and its product, nitric oxide (NO), and downregulated the secretion of pro-inflammatory cytokine and attenuated phagocytosis and bactericidal activities of macrophages to H. pylori. Furthermore, we identified that Jagged1, one of Notch signaling ligands, was both upregulated in mRNA and protein level in activated macrophages induced by H. pylori. Clinical specimens showed that the number of Jagged1+ macrophages in the stomach mucosa from H. pylori-infected patients was significantly higher than that in healthy control. The overexpression of Jagged1 promoted bactericidal activities of macrophages against H. pylori and siRNA-Jagged1 presented the opposite effect. Besides, the addition of exogenous rJagged1 facilitated the pro-inflammatory mediators of macrophages against H. pylori, but the treatment of anti-Jagged1 neutralizing antibody attenuated it. Taken together, these results suggest that Jagged1 is a promoting molecule for macrophages against H. pylori, which will provide insight for exploring Jagged1 as a novel therapeutic target for the control of H. pylori infection.
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影响因子：
16.6
作者：
Jiang H;Zhou C;Zhang Z;Wang Q;Wei H;Shi W;Li J;Wang Z;Ou Y;Wang W;Wang H;Zhang Q;Sun W;Sun P;Yang S
通讯作者：
Yang S
影响因子：
4.4
作者：
Kapoor, Nisha;Narayana, Yeddula;Balaji, Kithiganahalli N.
通讯作者：
Balaji, Kithiganahalli N.
影响因子：
3.1
作者：
Kaparakis, Maria;Walduck, Anna K.;Strugnell, Richard A.
通讯作者：
Strugnell, Richard A.
影响因子：
4.6
作者：
Hofmann, Jennifer J.;Briot, Anais;Iruela-Arispe, M. Luisa
通讯作者：
Iruela-Arispe, M. Luisa
影响因子：
4.5
作者：
Keewan, Esra'a;Naser, Saleh A.
通讯作者：
Naser, Saleh A.