禽多杀性巴氏杆菌通过抑制 Zyxin-FAK-AKT-FoxO1/NF-κB 轴诱导鸡巨噬细胞凋亡

IF 3.8 1区 农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Poultry Science Pub Date : 2024-11-02 DOI:10.1016/j.psj.2024.104504
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Subsequently, phalloidin staining of the F-actin assembly revealed that PmQ more significantly inhibited the formation of FAs in HD11 than PmCQ2. Western blot analysis revealed that the levels of Zyxin and phosphorylated focal adhesion kinase (FAK) were significantly decreased in PmQ-infected cells, confirming that PmQ inhibited FAs. Consequently, PmQ inhibited the FA downstream factor Akt, which decreased NF-κB and FoxO1 phosphorylation, as evidenced by the decreased expression of downstream anti-apoptotic genes (<em>GADD45B, BCL2L1, BCL2A1</em>, and <em>BIRC2</em>) and increased expression of downstream pro-apoptotic genes (<em>BCL6, PKL2, PKL3,</em> and <em>KLF2</em>). Conversely, pharmaceutically inhibiting FA formation using latrunculin A better enhanced PmCQ2-induced than PmQ-induced apoptosis in HD11 cells. Similarly, the knockdown of Zyxin or FoxO1 by siRNA both boosted the PmCQ2-induced apoptosis rates equal to those of PmQ. 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引用次数: 0

摘要

多杀性巴氏杆菌(P. multocida)可导致各种动物感染,尤其是家畜和家禽,从而给养殖业带来巨大损失。然而,禽多杀性巴氏杆菌的致病机理在很大程度上仍不为人所知。本研究探讨了禽类多杀霉素的致病机制。鸡巨噬细胞 HD11 细胞感染了禽株 PmQ 和牛株 PmCQ2。与PmCQ2相比,PmQ对HD11细胞诱导的细胞毒性和细胞凋亡更高,抗吞噬作用更强。RNA测序分析表明,与PmCQ2相比,PmQ感染的HD11细胞中局灶粘附(FA)相关基因明显下调。随后,对F-肌动蛋白组装的类胶体素染色显示,PmQ比PmCQ2更明显地抑制了HD11细胞中FA的形成。Western印迹分析显示,PmQ感染的细胞中Zyxin和磷酸化的焦点粘附激酶(FAK)水平明显下降,证实了PmQ抑制了FAs的形成。因此,PmQ 抑制了 FA 的下游因子 Akt,从而降低了 NF-κB 和 FoxO1 的磷酸化,下游抗凋亡基因(GADD45B、BCL2L1、BCL2A1 和 BIRC2)的表达量减少和下游促凋亡基因(BCL6、PKL2、PKL3 和 KLF2)的表达量增加就是证明。相反,在 HD11 细胞中,使用 latrunculin A 制药抑制 FA 的形成能更好地增强 PmCQ2 诱导的细胞凋亡,而不是 PmQ 诱导的细胞凋亡。同样,用 siRNA 敲除 Zyxin 或 FoxO1 都能提高 PmCQ2-诱导的细胞凋亡率,与 PmQ 相等。这些结果表明,PmQ抑制了Zyxin依赖的FA形成,并破坏了FAK-AKT-FoxO1/NF-κB通路,从而诱导鸡巨噬细胞凋亡。因此,本研究有助于深入了解禽类多杀霉素的致病机理,从而有助于开发新的抗多杀霉素感染的策略。
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Avian Pasteurella multocida induces chicken macrophage apoptosis by inhibiting the Zyxin-FAK-AKT-FoxO1/NF-κB axis
Pasteurella multocida (P. multocida) can cause infection in various animals, especially livestock and poultry, which can lead to substantial losses to the breeding industry. However, the pathogenesis of avian P. multocida remains largely unknown. In this study, the mechanisms of avian P. multocida pathogenesis were explored. Chicken macrophage HD11 cells were infected with the avian strain PmQ and the bovine strain PmCQ2. PmQ induced higher cytotoxicity and apoptosis and exerted a stronger anti-phagocytotic effect on HD11 cells than PmCQ2. RNA sequencing analysis revealed that focal adhesion (FA)-related genes were significantly downregulated in PmQ-infected HD11 cells compared with that of PmCQ2. Subsequently, phalloidin staining of the F-actin assembly revealed that PmQ more significantly inhibited the formation of FAs in HD11 than PmCQ2. Western blot analysis revealed that the levels of Zyxin and phosphorylated focal adhesion kinase (FAK) were significantly decreased in PmQ-infected cells, confirming that PmQ inhibited FAs. Consequently, PmQ inhibited the FA downstream factor Akt, which decreased NF-κB and FoxO1 phosphorylation, as evidenced by the decreased expression of downstream anti-apoptotic genes (GADD45B, BCL2L1, BCL2A1, and BIRC2) and increased expression of downstream pro-apoptotic genes (BCL6, PKL2, PKL3, and KLF2). Conversely, pharmaceutically inhibiting FA formation using latrunculin A better enhanced PmCQ2-induced than PmQ-induced apoptosis in HD11 cells. Similarly, the knockdown of Zyxin or FoxO1 by siRNA both boosted the PmCQ2-induced apoptosis rates equal to those of PmQ. These results demonstrated that PmQ inhibited Zyxin-dependent FA formation and disrupted the FAK-AKT-FoxO1/NF-κB pathway to induce apoptosis in chicken macrophages. This study thus offers insights into the pathogenesis of avian P. multocida, which could facilitate the development of new strategies against P. multocida infection.
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来源期刊
Poultry Science
Poultry Science 农林科学-奶制品与动物科学
CiteScore
7.60
自引率
15.90%
发文量
0
审稿时长
94 days
期刊介绍: First self-published in 1921, Poultry Science is an internationally renowned monthly journal, known as the authoritative source for a broad range of poultry information and high-caliber research. The journal plays a pivotal role in the dissemination of preeminent poultry-related knowledge across all disciplines. As of January 2020, Poultry Science will become an Open Access journal with no subscription charges, meaning authors who publish here can make their research immediately, permanently, and freely accessible worldwide while retaining copyright to their work. Papers submitted for publication after October 1, 2019 will be published as Open Access papers. An international journal, Poultry Science publishes original papers, research notes, symposium papers, and reviews of basic science as applied to poultry. This authoritative source of poultry information is consistently ranked by ISI Impact Factor as one of the top 10 agriculture, dairy and animal science journals to deliver high-caliber research. Currently it is the highest-ranked (by Impact Factor and Eigenfactor) journal dedicated to publishing poultry research. Subject areas include breeding, genetics, education, production, management, environment, health, behavior, welfare, immunology, molecular biology, metabolism, nutrition, physiology, reproduction, processing, and products.
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