梅毒螺旋体在体外通过BiP-PERK-COX-2信号通路上调前列腺素E2抑制巨噬细胞吞噬功能

doi:10.3969/j.issn.1673-8640.2026.06.010

检验医学 ›› 2026, Vol. 41 ›› Issue (6): 583-589.DOI: 10.3969/j.issn.1673-8640.2026.06.010

梅毒螺旋体在体外通过BiP-PERK-COX-2信号通路上调前列腺素E2抑制巨噬细胞吞噬功能

益董雨¹, 陈蓉², 李娜³, 沈振华⁴()

¹ 上海中医药大学附属第七人民医院医学检验科，上海 200137
² 上海市临床检验中心，上海 200126
³ 海军特色医学中心，上海 200433
⁴ 上海市浦东新区公利医院，上海 200135

收稿日期:2025-10-12 修回日期:2025-12-24 出版日期:2026-06-30 发布日期:2026-07-01
通讯作者: 沈振华，E-mail：shen_zhenhua@sina.com。
作者简介:益董雨，男，1998年生，硕士，检验技师，主要从事梅毒螺旋体致病机制研究；
陈蓉，女，1979年生，学士，副主任技师，主要从事临床微生物检验质量控制工作。第一联系人：
益董雨和陈蓉对本研究具有同等贡献，并列为第一作者。
基金资助:
上海市浦东新区卫生系统重点学科群建设项目(PWZxq2022-08);上海中医药大学附属第七人民医院人才培养计划(JY2025-02)

Treponema pallidum upregulates prostaglandin E2 through BiP-PERK-COX-2 signaling pathway in vitro to inhibit the phagocytosis of macrophages

YI Dongyu¹, CHEN Rong², LI Na³, SHEN Zhenhua⁴()

¹ Department of Clinical Laboratory， the Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine， Shanghai 200137， China
² Shanghai Center for Clinical Laboratory， Shanghai 200126， China
³ Naval Medical Center， Shanghai 200433， China
⁴ Gongli Hospital of Pudong New Area， Shanghai 200135， China

Received:2025-10-12 Revised:2025-12-24 Online:2026-06-30 Published:2026-07-01

摘要/Abstract

摘要：

目的分析梅毒螺旋体对巨噬细胞吞噬功能的影响，以及这种影响是否通过调控前列腺素E2分泌的相关通路实现。方法用佛波酯（PMA）诱导人单核细胞系 THP-1 分化为巨噬细胞，作为主要细胞实验模型。采用荧光微球吞噬实验检测巨噬细胞的吞噬功能。采用酶联免疫吸附试验（ELISA）检测细胞培养上清液中前列腺素E2的分泌水平。采用免疫印迹法检测内质网应激标志蛋白BiP、PERK、COX-2的表达。采用BiP抑制剂、PERK抑制剂、COX-2抑制剂、前列腺素E2抗体进行干预实验，验证梅毒螺旋体通过激活BiP-PERK-COX-2信号通路上调前列腺素E2抑制巨噬细胞吞噬功能。结果梅毒螺旋体以浓度依赖的方式显著抑制巨噬细胞吞噬荧光微球。梅毒螺旋体诱导巨噬细胞分泌前列腺素E2，前列腺素E2抗体能够逆转梅毒螺旋体引起的吞噬抑制。BiP抑制剂、PERK抑制剂和COX-2抑制剂均能有效抑制前列腺素E2的产生，并恢复巨噬细胞的吞噬功能。结论梅毒螺旋体在体外通过激活BiP-PERK-COX-2信号通路上调前列腺素E2，抑制巨噬细胞吞噬功能。

关键词: 梅毒螺旋体, 巨噬细胞, 吞噬, 前列腺素E2

Abstract:

Objective To analyze the effect of Treponema pallidum on the phagocytosis of macrophages and whether this effect is achieved through the regulation of prostaglandin E2 secretion pathway. Methods Human monocytic cell line THP-1 was differentiated into macrophages by phorbol myristate acetate（PMA） as the main cell experimental model. The phagocytosis of macrophages was determined by fluorescent microsphere phagocytosis assay. The secretion level of prostaglandin E2 in the cell supernatant was determined by enzyme-linked immunosorbent assay（ELISA）. The expression of endoplasmic reticulum stress marker proteins（BiP，PERK and COX-2） was determined by western blotting. BiP inhibitor，PERK inhibitor，COX-2 inhibitor and prostaglandin E2 antibody were used for intervention experiments to verify whether Treponema pallidum inhibited the phagocytosis of macrophages by upregulating prostaglandin E2 through the activation of BiP-PERK-COX-2 signaling pathway. Results Treponema pallidum inhibited the phagocytosis of fluorescent microspheres by macrophages in a concentration-dependent manner. Treponema pallidum induced the secretion of prostaglandin E2 by macrophages，and the use of prostaglandin E2 antibody could reverse the phagocytosis inhibition caused by Treponema pallidum. BiP inhibitor，PERK inhibitor and COX-2 inhibitor could all effectively inhibit the production of prostaglandin E2 and restore the phagocytosis of macrophages. Conclusions Treponema pallidum inhibits the phagocytosis of macrophages in vitro by upregulating prostaglandin E2 through the activation of BiP-PERK-COX-2 signaling pathway.

Key words: Treponema pallidum, Macrophage, Phagocytosis, Prostaglandin E2

中图分类号:

R377

益董雨, 陈蓉, 李娜, 沈振华. 梅毒螺旋体在体外通过BiP-PERK-COX-2信号通路上调前列腺素E2抑制巨噬细胞吞噬功能[J]. 检验医学, 2026, 41(6): 583-589.

YI Dongyu, CHEN Rong, LI Na, SHEN Zhenhua. Treponema pallidum upregulates prostaglandin E2 through BiP-PERK-COX-2 signaling pathway in vitro to inhibit the phagocytosis of macrophages[J]. Laboratory Medicine, 2026, 41(6): 583-589.

图/表 5

图1 梅毒螺旋体抑制巨噬细胞吞噬乳胶微球注：绿色为乳胶微球；与PBS比较*P<0.05，**P<0.001。

图2 梅毒螺旋体通过前列腺素E2抑制巨噬细胞吞噬乳胶微球注：（a）梅毒螺旋体诱导巨噬细胞分泌前列腺素E2的浓度；与PBS比较，**P<0.001；（b）抗体中和后巨噬细胞吞噬乳胶微球的流式细胞分析结果；（c）抗体中和后巨噬细胞吞噬乳胶微球的荧光圈；绿色为乳胶微球。

图3 梅毒螺旋体通过COX-2诱导前列腺素E2表达注：（a）梅毒螺旋体促进巨噬细胞表达COX-2蛋白；（b）梅毒螺旋体通过COX-2蛋白诱导巨噬细胞表达前列腺素E2。

图4 梅毒螺旋体通过BiP-PERK-COX-2通路诱导前列腺素E2表达注：（a）HA-15干预下梅毒螺旋体对BiP、PERK和COX-2蛋白表达的调整；（b）GSK干预下梅毒螺旋体对PERK和COX-2蛋白表达的调整；（c）HA-15和GSK对梅毒螺旋体诱导前列腺素E2分泌的影响。

图5 抑制BiP-PERK-COX-2通路可逆转梅毒螺旋体对吞噬功能的抑制注：绿色为乳胶微球。

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梅毒螺旋体在体外通过BiP-PERK-COX-2信号通路上调前列腺素E2抑制巨噬细胞吞噬功能

Treponema pallidum upregulates prostaglandin E2 through BiP-PERK-COX-2 signaling pathway in vitro to inhibit the phagocytosis of macrophages

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