金黄色葡萄球菌脂蛋白对奶牛骨髓源巨噬细胞炎症介质分泌及前列腺素E2合成分泌的影响

doi:10.11843/j.issn.0366-6964.2025.07.039

畜牧兽医学报 ›› 2025, Vol. 56 ›› Issue (7): 3474-3483.doi: 10.11843/j.issn.0366-6964.2025.07.039

金黄色葡萄球菌脂蛋白对奶牛骨髓源巨噬细胞炎症介质分泌及前列腺素E2合成分泌的影响

刘谕泽(), 于琢雅(), 巩志国, 任佩佩, 赵佳敏, 毛伟, 张双翼*(), 冯爽*()

内蒙古农业大学兽医学院，呼和浩特 010018

收稿日期:2024-09-12 出版日期:2025-07-23 发布日期:2025-07-25
通讯作者: 张双翼,冯爽 E-mail:2516758527@qq.com;17704884830@163.com;shuangyisyau@163.com;fairysshuang@163.com
作者简介:刘谕泽(1999-)，内蒙古鄂尔多斯人，硕士生，主要从事兽医临床内科学研究，E-mail：2516758527@qq.com
于琢雅(1997-)，黑龙江双鸭山人，硕士生，主要从事兽医临床内科学研究，E-mail：17704884830@163.com
第一联系人：
刘谕泽和于琢雅为同等贡献作者
基金资助:
国家自然科学基金(32260903；32202879)；内蒙古自治区研究生科研创新资助项目(S20231098Z)

The Impact of Lipoprotein on the Secretion of Inflammatory Mediators and the Synthesis of Prostaglandin E2 in Bovine Bone Marrow-derived Macrophages Infected with Staphylococcus aureus

LIU Yuze(), YU Zhuoya(), GONG Zhiguo, REN Peipei, ZHAO Jiamin, MAO Wei, ZHANG Shuangyi*(), FENG Shuang*()

College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, China

Received:2024-09-12 Online:2025-07-23 Published:2025-07-25
Contact: ZHANG Shuangyi, FENG Shuang E-mail:2516758527@qq.com;17704884830@163.com;shuangyisyau@163.com;fairysshuang@163.com

摘要/Abstract

摘要：

金黄色葡萄球菌(Staphylococcus aureus，S aureus)在侵入哺乳动物体内时会引起宿主炎症反应，但金葡菌脂蛋白对细胞因子的释放以及PGE₂的合成是否具有影响目前尚不明确。本研究使用金黄色葡萄球菌SA113及其脂蛋白缺失菌株和回复菌株感染奶牛骨髓源巨噬细胞后，探究金黄色葡萄球菌脂蛋白在诱导免疫细胞炎症介质及PGE₂的分泌合成中的作用机制。试验结果表明，与SA113感染组相比，金葡菌敲除株Δlgt感染奶牛骨髓源巨噬细胞后PGE₂分泌水平发生显著下降，同时促炎性细胞因子(TNF-α和IL-1β)和抗炎因子(IL-10)的分泌水平均发生显著下降。Western blot结果表明，金黄色葡萄球菌脂蛋白对巨噬细胞NF-κB/MAPK通路激活以及PGE₂合成酶COX-2和mPGES-1的表达具有影响。此外，金黄色葡萄球菌脂蛋白缺失后巨噬细胞中TLR2、TLR4和NLRP3基因表达水平发生显著降低。综上所述，在金葡菌感染过程中，金葡菌脂蛋白对巨噬细胞炎症信号通路的激活，所介导的炎症介质的分泌具有重要作用，且与PGE₂的合成与分泌存在紧密联系。该研究可为兽医临床应用前列腺素合成酶抑制剂和非甾体抗炎药防治金葡菌感染性疾病提供理一定的理论依据。

关键词: 金黄色葡萄球菌, 奶牛骨髓源巨噬细胞, PGE₂, 脂蛋白, 细胞因子

Abstract:

Staphylococcus aureus (S. aureus) triggers an inflammatory response in the host upon invading mammalian systems, but the role of its lipoproteins in cytokine release and PGE₂ synthesis remains unclear. This study used the S. aureus SA113 strain, its lipoprotein-deficient mutant, and the complemented strain to infect bovine bone marrow-derived macrophages (bBMMs), aiming to investigate the role of S. aureus lipoproteins in stimulating cytokine release and PGE₂ production in immune cells. In this study, the mechanism of action of S. aureus lipoprotein in inducing the secretion and synthesis of immune cell inflammatory mediators and PGE₂ by infecting bovine bone marrow-derived macrophages with SA113, S. aureus SA113 isogenic mutant lgt: : ermB (Δlgt) deficient in lipoprotein maturation, and its complemented strain SA113 lgt: : ermB +pRBlgt (+pRB). The results showed that compared to the SA113-infected group, the secretion level of PGE₂ significantly decreased after infecting bBMMs with the S. aureus Δlgt mutant, while the secretion levels of pro-inflammatory cytokines (TNF-α and IL-1β) and anti-inflammatory cytokine (IL-10) also significantly decreased. Western blot results indicated that S. aureus lipoprotein influenced the activation of the NF-κB/MAPK pathway in bBMMs and the expression of PGE₂ synthetic enzymes COX-2 and mPGES-1. In addition, the expression levels of TLR2, TLR4 and NLRP3 genes in bBMMs were significantly reduced after loss of S. aureus lipoprotein. In conclusion, during S. aureus infection, S. aureus lipoprotein plays a significant role in activating macrophage inflammatory signaling pathways, mediating the secretion of inflammatory mediators, and it is closely associated with the synthesis and secretion of PGE₂. This study offers a theoretical foundation for the clinical use of prostaglandin synthetase inhibitors and non-steroidal anti-inflammatory drugs (NSAIDs) to prevent and treat infections from S. aureus.

Key words: Staphylococcus aureus, bovine bone marrow-derived macrophages, prostaglandin E2, lipoprotein, cytokines

中图分类号:

S859.7

刘谕泽, 于琢雅, 巩志国, 任佩佩, 赵佳敏, 毛伟, 张双翼, 冯爽. 金黄色葡萄球菌脂蛋白对奶牛骨髓源巨噬细胞炎症介质分泌及前列腺素E2合成分泌的影响[J]. 畜牧兽医学报, 2025, 56(7): 3474-3483.

LIU Yuze, YU Zhuoya, GONG Zhiguo, REN Peipei, ZHAO Jiamin, MAO Wei, ZHANG Shuangyi, FENG Shuang. The Impact of Lipoprotein on the Secretion of Inflammatory Mediators and the Synthesis of Prostaglandin E2 in Bovine Bone Marrow-derived Macrophages Infected with Staphylococcus aureus[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(7): 3474-3483.

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引物名称 Primer name	GenBank登录号 GenBank accession No	引物序列 Primer sequences
β-actin	NM_173979.3	Forward 5′-TCACCAACTGGGACGACA-3′
		Reverse 5′-GCATACAGGGACAGCACA-3′
TLR2	NM_174197.2	Forward 5′-CGATGACTACCGCTGTGACTC-3′
		Reverse 5′-CCTTCCTGGGCTTCCTCTT-3′
TLR4	NM_174198.6	Forward: 5′-TGCCTTCACTACAGGGACTTT-3′
		Reverse: 5′-TGGGACACCACGACAATAAC-3′
NLRP3	NM_001102219.1	Forward: 5′-CAGATGAGCAGCAAGCAAGG-3′
		Reverse: 5′-ACAATCCAGCAGACCAGAGG-3′
COX-2	XM_007115297.3	Forward: 5′-GGTGCCTGGTCTGATGATGT-3′
		Reverse: 5′-GATTAGCCTGCTTGTCTGGAAC-3′
mPGES-1	XM_027556544.1	Forward: 5′-ATGGTACACACCGTGGCATA-3′
		Reverse: 5′-CACAATCTCAAAGGGCCATC-3′

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金黄色葡萄球菌脂蛋白对奶牛骨髓源巨噬细胞炎症介质分泌及前列腺素E2合成分泌的影响

The Impact of Lipoprotein on the Secretion of Inflammatory Mediators and the Synthesis of Prostaglandin E2 in Bovine Bone Marrow-derived Macrophages Infected with Staphylococcus aureus

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