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AvrA 通过抑制 p-JNK 和 Beclin-1 分子对其原始血清型发挥 NF-κB 通路抑制作用。

AvrA Exerts Inhibition of NF-κB Pathway in Its Naïve Serotype through Suppression of p-JNK and Beclin-1 Molecules.

机构信息

Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-Food Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou 225009, China.

Jiangsu Key Lab of Zoonosis/Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China.

出版信息

Int J Mol Sci. 2020 Aug 23;21(17):6063. doi: 10.3390/ijms21176063.

Abstract

Avian salmonellosis caused by serovar Enteritidis (. Enteritidis) and Pullorum ( Pullorum) remains a big threat to the poultry industry and public hygiene. AvrA is an effector involved in inhibiting inflammation. Compared to AvrA from . Enteritidis (SE-AvrA), the AvrA from Pullorum (SP-AvrA) lacks ten amino acids at the C-terminal. In this study, we compared the anti-inflammatory response induced by SP-AvrA to that of SE-AvrA. Transient expression of SP-AvrA in epithelial cells resulted in significantly weaker inhibition of NF-κB pathway activation when treated with TNF-α compared to the inhibition by SE-AvrA. SP-AvrA expression in the . Enteritidis resulted in weaker suppression of NF-κB pathway in infected HeLa cells compared to SE-AvrA expression in the cells, while SP-AvrA expressed in Pullorum C79-13 suppressed NF-κB activation in infected HeLa and Caco 2 BBE cells to a greater extent than did SE-AvrA because of the higher expression of SP-AvrA than SE-AvrA in Pullorum. Further analysis demonstrated that the inhibition of NF-κB pathway in -infected cells corresponded to the downregulation of the p-JNK and Beclin-1 protein molecules. Our study reveals that AvrA modifies the anti-inflammatory response in a manner dependent on the serotype through inhibition of NF-κB pathway.

摘要

肠炎沙门氏菌(肠炎亚种)和鸡白痢沙门氏菌(鸡白痢亚种)引起的禽类沙门氏菌病仍然是家禽业和公共卫生的一大威胁。AvrA 是一种参与抑制炎症的效应子。与肠炎亚种的 AvrA(SE-AvrA)相比,鸡白痢亚种的 AvrA(SP-AvrA)在 C 末端缺少十个氨基酸。在本研究中,我们比较了 SP-AvrA 诱导的抗炎反应与 SE-AvrA 的抗炎反应。与 SE-AvrA 相比,SP-AvrA 在肠上皮细胞中的瞬时表达导致在 TNF-α处理时对 NF-κB 途径激活的抑制作用明显减弱。与 SE-AvrA 在细胞中的表达相比,鸡白痢亚种中的 SP-AvrA 表达导致感染的 HeLa 细胞中 NF-κB 途径的抑制作用减弱,而鸡白痢亚种中表达的 SP-AvrA 对感染的 HeLa 和 Caco 2 BBE 细胞中 NF-κB 激活的抑制作用要强于 SE-AvrA,因为 SP-AvrA 在鸡白痢亚种中的表达高于 SE-AvrA。进一步分析表明,感染细胞中 NF-κB 途径的抑制与 p-JNK 和 Beclin-1 蛋白分子的下调相对应。我们的研究表明,AvrA 通过抑制 NF-κB 途径,以依赖血清型的方式修饰抗炎反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e86d/7504150/99f879cf3e08/ijms-21-06063-g002.jpg

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