Simin Lu , Jianye Wang , Zhangping He , Siqin He , Kang Zheng , Man Xu , Shuai Yuan , Yimou Wu
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The integrity of blood-brain barrier model was evaluated by a transendothelial cell resistance meter and transmission electron microscope after the stimulation of recombinant protein TP0751. Hoechst 33258 staining and flow cytometry were used to detect the apoptosis rate. Western blotting assay was used to measure the expression of tight junction proteins and apoptosis-related proteins. The enzyme activity detection kit was responsible for detecting the enzyme activities of Caspase 3, Caspase 8 and Caspase 9. The expression of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 at the transcription and translation levels were detected by qRT-PCR and ELISA, respectively.</p></div><div><h3>Results</h3><p>The results showed that, the tight junction structures between cells showed no obvious fragmentation, but the levels of the tight junction proteins zonula occludens-1 and occludin were reduced by the effects of Tp0751 on bEnd3 cells. In addition, further research demonstrated that after incubation with bEnd3 cells, Tp0751 induced cell apoptosis in a concentration- and time-dependent manner via the caspase 8/caspase 3 pathway. These apoptotic processes may have contributed to the changes in tight junction proteins expression. Furthermore, the Tp0751 protein may be involved in the pathogenic process by which <em>T. pallidum</em> crosses the blood-brain barrier by promoting secretion of the proinflammatory factor interleukin-6.</p></div><div><h3>Conclusions</h3><p>On the whole, this study is the first to reveal and highlight that Tp0751 may affect the expression of tight junction proteins by inducing apoptosis and promoting the secretion of the inflammatory cytokine IL-6, thus playing a role in the progression of neurosyphilis caused by <em>T. pallidum</em>.</p></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"312 4","pages":"Article 151553"},"PeriodicalIF":4.5000,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1438422122000066/pdfft?md5=23b7e00b78977ae4c73e783709fe8c3f&pid=1-s2.0-S1438422122000066-main.pdf","citationCount":"5","resultStr":"{\"title\":\"Treponema pallidum Tp0751 alters the expression of tight junction proteins by promoting bEnd3 cell apoptosis and IL-6 secretion\",\"authors\":\"Simin Lu , Jianye Wang , Zhangping He , Siqin He , Kang Zheng , Man Xu , Shuai Yuan , Yimou Wu\",\"doi\":\"10.1016/j.ijmm.2022.151553\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Neurosyphilis is a serious complication caused by the invasion of the central nervous system by <em>Treponema pallidum subsp. pallidum</em> (<em>T. pallidum</em>). However, the molecular mechanism by which <em>T. pallidum</em> crosses the blood-brain barrier has not been fully elucidated.</p></div><div><h3>Objectives</h3><p>The primary purpose of this experimental design was to explore the effect of the <em>T. pallidum</em> adhesion protein Tp0751 on the blood-brain barrier and cerebrovascular endothelial cells.</p></div><div><h3>Methods</h3><p>BEnd3 cells were used to construct a monolayer blood-brain barrier model in vitro. The integrity of blood-brain barrier model was evaluated by a transendothelial cell resistance meter and transmission electron microscope after the stimulation of recombinant protein TP0751. Hoechst 33258 staining and flow cytometry were used to detect the apoptosis rate. Western blotting assay was used to measure the expression of tight junction proteins and apoptosis-related proteins. The enzyme activity detection kit was responsible for detecting the enzyme activities of Caspase 3, Caspase 8 and Caspase 9. 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Treponema pallidum Tp0751 alters the expression of tight junction proteins by promoting bEnd3 cell apoptosis and IL-6 secretion
Background
Neurosyphilis is a serious complication caused by the invasion of the central nervous system by Treponema pallidum subsp. pallidum (T. pallidum). However, the molecular mechanism by which T. pallidum crosses the blood-brain barrier has not been fully elucidated.
Objectives
The primary purpose of this experimental design was to explore the effect of the T. pallidum adhesion protein Tp0751 on the blood-brain barrier and cerebrovascular endothelial cells.
Methods
BEnd3 cells were used to construct a monolayer blood-brain barrier model in vitro. The integrity of blood-brain barrier model was evaluated by a transendothelial cell resistance meter and transmission electron microscope after the stimulation of recombinant protein TP0751. Hoechst 33258 staining and flow cytometry were used to detect the apoptosis rate. Western blotting assay was used to measure the expression of tight junction proteins and apoptosis-related proteins. The enzyme activity detection kit was responsible for detecting the enzyme activities of Caspase 3, Caspase 8 and Caspase 9. The expression of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 at the transcription and translation levels were detected by qRT-PCR and ELISA, respectively.
Results
The results showed that, the tight junction structures between cells showed no obvious fragmentation, but the levels of the tight junction proteins zonula occludens-1 and occludin were reduced by the effects of Tp0751 on bEnd3 cells. In addition, further research demonstrated that after incubation with bEnd3 cells, Tp0751 induced cell apoptosis in a concentration- and time-dependent manner via the caspase 8/caspase 3 pathway. These apoptotic processes may have contributed to the changes in tight junction proteins expression. Furthermore, the Tp0751 protein may be involved in the pathogenic process by which T. pallidum crosses the blood-brain barrier by promoting secretion of the proinflammatory factor interleukin-6.
Conclusions
On the whole, this study is the first to reveal and highlight that Tp0751 may affect the expression of tight junction proteins by inducing apoptosis and promoting the secretion of the inflammatory cytokine IL-6, thus playing a role in the progression of neurosyphilis caused by T. pallidum.
期刊介绍：
Pathogen genome sequencing projects have provided a wealth of data that need to be set in context to pathogenicity and the outcome of infections. In addition, the interplay between a pathogen and its host cell has become increasingly important to understand and interfere with diseases caused by microbial pathogens. IJMM meets these needs by focussing on genome and proteome analyses, studies dealing with the molecular mechanisms of pathogenicity and the evolution of pathogenic agents, the interactions between pathogens and host cells ("cellular microbiology"), and molecular epidemiology. To help the reader keeping up with the rapidly evolving new findings in the field of medical microbiology, IJMM publishes original articles, case studies and topical, state-of-the-art mini-reviews in a well balanced fashion. All articles are strictly peer-reviewed. Important topics are reinforced by 2 special issues per year dedicated to a particular theme. Finally, at irregular intervals, current opinions on recent or future developments in medical microbiology are presented in an editorial section.
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