Mycoplasma genitalium Protein of Adhesion Induces Inflammatory Cytokines via Cyclophilin A-CD147 Activating the ERK-NF-κB Pathway in Human Urothelial Cells.
Mycoplasma genitalium Protein of Adhesion Induces Inflammatory Cytokines via Cyclophilin A-CD147 Activating the ERK-NF-κB Pathway in Human Urothelial Cells.
复制标题
生殖支原体粘附蛋白通过亲环蛋白 A-CD147 激活人尿路上皮细胞中的 ERK-NF-κB 途径诱导炎症细胞因子
DOI：
10.3389/fimmu.2020.02052
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发表时间：
2020
影响因子：
7.3
通讯作者：
Zeng Y
中科院分区：
文献类型：
--
作者：
Li L;Luo D;Liao Y;Peng K;Zeng Y
生殖支原体粘附蛋白(MgPa)在生殖支原体粘附和侵袭宿主细胞的过程中发挥重要作用，对其在宿主细胞中的致病机制具有重要意义。我们之前的研究表明，亲环蛋白 A (CypA) 是人尿路上皮细胞 (SV-HUC-1) 中 MgPa 的受体，因此可以通过与 MgPa 相互作用介导生殖支原体对宿主细胞的粘附和侵袭。然而，生殖支原体对宿主细胞的具体发病机制以及MgPa和CypA相互作用的可能致病机制尚未阐明。该研究旨在阐明 MgPa 的致病机制。通过 ELISA 检测 SV-HUC-1 细胞中重组 MgPa (rMgPa) 诱导的细胞外 CypA (eCypA)，并使用共定位和免疫共沉淀测定验证 CypA 和 CD147 之间的相互作用。此外，还证实了 rMgPa 诱导的 eCypA 引起的细胞外信号调节激酶 (ERK) 磷酸化和 NF-κB 激活。本研究结果证实rMgPa可诱导SV-HUC-1细胞分泌eCypA，从而通过CypA-CD147相互作用促进IL-1β、IL-6、TNF-α和MMP-9的蛋白和mRNA表达，从而激活ERK-NF-κB通路，有利于阐明生殖支原体对宿主细胞的发病机制和可能的致病机制。
Mycoplasma genitalium protein of adhesion (MgPa) plays an important role in the process of adhesion and invasion of host cells by M. genitalium, and is thus significant for its pathogenic mechanisms in host cells. Our previous study has demonstrated that cyclophilin A (CypA) is the receptor for MgPa in human urothelial cells (SV-HUC-1) and can, therefore, mediate the adherence and invasion of M. genitalium into host cells by interacting with MgPa. However, the specific pathogenesis of M. genitalium to host cells and the possible pathogenic mechanism involved in the interaction of MgPa and CypA have never been clarified. The study aimed to elucidate the mechanism involved in the pathogenicity of MgPa. Recombinant MgPa (rMgPa) induced extracellular CypA (eCypA) was detected in SV-HUC-1 cells by ELISA, and the interaction between CypA and CD147 was validated using co-localization and co-immunoprecipitation assay. In addition, both extracellular signal-regulated kinases (ERK) phosphorylation and NF-κB activation evoked by rMgPa-induced eCypA were also demonstrated. The findings of this study verified that rMgPa could induce the secretion of eCypA in SV-HUC-1 cells and thus promote the protein and mRNA expression of IL-1β, IL-6, TNF-α and MMP-9 via CypA-CD147 interaction and thus activating ERK-NF-κB pathway, which is beneficial to elucidate the pathogenesis and possible pathogenic mechanism of M. genitalium to host cells.