{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:33:01Z","timestamp":1789623181345,"version":"build-2803163510"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2022JJ30532"],"award-info":[{"award-number":["2022JJ30532"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009020","name":"University of South China Innovation Foundation for Postgraduate","doi-asserted-by":"publisher","award":["213YXC016"],"award-info":[{"award-number":["213YXC016"]}],"id":[{"id":"10.13039\/501100009020","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009020","name":"University of South China Innovation Foundation for Postgraduate","doi-asserted-by":"publisher","award":["2022JJ40396"],"award-info":[{"award-number":["2022JJ40396"]}],"id":[{"id":"10.13039\/501100009020","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Neutrophils are essential cells involved in inflammation. However, the specific mechanism of neutrophil chemotaxis induced by Treponema pallidum remains unknown. In this study, human umbilical vein endothelial cells (HUVECs) were utilized as target cells to investigate the expression levels of chemokines when stimulated with different concentrations of Tp0768 (also known as TpN44.5 or TmpA, a T. pallidum infection dependent antigen). The results indicated that Tp0768 treatment enhanced neutrophil chemotaxis in HUVECs, which was closely associated with the expression levels of CXCL1, CXCL2, and CXCL8 (also known as interleukin-8). At the same time, the results show that the Toll-like receptor 2 (TLR2) signaling pathway is activated and that endoplasmic reticulum (ER) stress occurs. Furthermore, the findings revealed that the use of protein kinase RNA-like endoplasmic reticulum kinase (PERK) and immunoglobulin-regulated enhancer 1 (IRE1) inhibitors reduced the expression levels of CXCL1, CXCL2, and CXCL8. Additionally, inhibiting TLR2 significantly decreased the expression levels of ER stress\u2013related proteins (PERK and IRE1), CXCL1, CXCL2, and CXCL8. Consequently, neutrophil chemotaxis was significantly inhibited after treatment with TLR2, PERK, and IRE1 inhibitors. These findings shed light on the role of Tp0768 in enhancing neutrophil chemotaxis in endothelial cells, providing a foundation for further exploration of syphilis pathogenesis and offering a new direction for the diagnosis and treatment of T. pallidum infection.<\/jats:p>","DOI":"10.1093\/jleuko\/qiae114","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T17:38:59Z","timestamp":1715794739000},"page":"1045-1053","source":"Crossref","is-referenced-by-count":7,"title":["<i>Treponema pallidum<\/i> recombinant protein Tp0768 enhances the ability of HUVECs to promote neutrophil chemotaxis through the TLR2\/ER stress signaling pathway"],"prefix":"10.1093","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5436-6724","authenticated-orcid":false,"given":"Ting","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-Incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China , No.69, Chuanshang Road, Hengyang 421001, Hunan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-Incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China , No.69, Chuanshang Road, Hengyang 421001, Hunan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangping","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-Incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China , No.69, Chuanshang Road, Hengyang 421001, Hunan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0211-7360","authenticated-orcid":false,"given":"Yun","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-Incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China , No.69, Chuanshang Road, Hengyang 421001, Hunan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bisha","family":"He","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-Incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China , No.69, Chuanshang Road, Hengyang 421001, Hunan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-Incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China , No.69, Chuanshang Road, Hengyang 421001, Hunan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibao","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-Incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China , No.69, Chuanshang Road, Hengyang 421001, Hunan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"En","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-Incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China , No.69, Chuanshang Road, Hengyang 421001, Hunan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-Incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China , No.69, Chuanshang Road, Hengyang 421001, Hunan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3196-7843","authenticated-orcid":false,"given":"Xiaoping","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-Incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China , No.69, Chuanshang Road, Hengyang 421001, Hunan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feijun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Pathogenic Biology and Key Laboratory of Special Pathogen Prevention and Control of Hunan Province, Hengyang Medical College, University of South China , No.28, Changsheng West Road, Hengyang 421001 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopeng","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-Incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China , No.69, Chuanshang Road, Hengyang 421001, Hunan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2690-2665","authenticated-orcid":false,"given":"Shuangquan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-Incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China , No.69, Chuanshang Road, Hengyang 421001, Hunan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"issue":"1","key":"2024110323521417200_qiae114-B1","doi-asserted-by":"publisher","first-page":"17073","DOI":"10.1038\/nrdp.2017.73","article-title":"Syphilis","volume":"3","author":"Peeling","year":"2017","journal-title":"Nat Rev Dis Primers"},{"issue":"1","key":"2024110323521417200_qiae114-B2","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1128\/CMR.19.1.29-49.2006","article-title":"Biological basis for syphilis","volume":"19","author":"Lafond","year":"2006","journal-title":"Clin Microbiol Rev"},{"key":"2024110323521417200_qiae114-B3","first-page":"327","article-title":"Experimental mouse syphilis; organ distribution of the infectious agent","volume":"32","author":"Rosahn","year":"1948","journal-title":"Am J Syph Gonorrhea Vener Dis"},{"issue":"6","key":"2024110323521417200_qiae114-B4","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1111\/1523-1747.ep12524230","article-title":"Host response to Treponema pallidum in intradermally-infected rabbits: evidence for persistence of infection at local and distant sites","volume":"75","author":"Sell","year":"1980","journal-title":"J Invest Dermatol"},{"issue":"4","key":"2024110323521417200_qiae114-B5","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/S0002-9343(89)80826-5","article-title":"Cardiovascular syphilis","volume":"87","author":"Jackman","year":"1989","journal-title":"Am J Med"},{"issue":"7","key":"2024110323521417200_qiae114-B6","doi-asserted-by":"publisher","first-page":"e24788","DOI":"10.1097\/MD.0000000000024788","article-title":"Cardiovascular syphilis-associated acute myocardial infarction: a case report","volume":"100","author":"Li","year":"2021","journal-title":"Medicine (Baltimore)"},{"issue":"1","key":"2024110323521417200_qiae114-B7","doi-asserted-by":"publisher","first-page":"e000418","DOI":"10.1136\/lupus-2020-000418","article-title":"Lupus serum induces inflammatory interaction with neutrophils in human glomerular endothelial cells","volume":"7","author":"Russell","year":"2020","journal-title":"Lupus Sci Med"},{"issue":"3","key":"2024110323521417200_qiae114-B8","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1007\/s00441-017-2776-8","article-title":"Neutrophil chemotaxis","volume":"371","author":"Petri","year":"2018","journal-title":"Cell Tissue Res"},{"issue":"6","key":"2024110323521417200_qiae114-B9","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1038\/nri.2016.49","article-title":"Neutrophil migration in infection and wound repair: going forward in reverse","volume":"16","author":"de Oliveira","year":"2016","journal-title":"Nat Rev Immunol"},{"issue":"24","key":"2024110323521417200_qiae114-B10","doi-asserted-by":"publisher","first-page":"4930","DOI":"10.1182\/blood-2013-02-486217","article-title":"Mast cell and macrophage chemokines CXCL1\/CXCL2 control the early stage of neutrophil recruitment during tissue inflammation","volume":"121","author":"De Filippo","year":"2013","journal-title":"Blood"},{"issue":"3","key":"2024110323521417200_qiae114-B11","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/s41423-023-00974-6","article-title":"The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention","volume":"20","author":"Cambier","year":"2023","journal-title":"Cell Mol Immunol"},{"issue":"7","key":"2024110323521417200_qiae114-B12","doi-asserted-by":"publisher","first-page":"1875","DOI":"10.1089\/ars.2010.3723","article-title":"Toll-like receptors: new players in myocardial ischemia\/reperfusion injury","volume":"15","author":"Ha","year":"2011","journal-title":"Antioxid Redox Signal"},{"issue":"9","key":"2024110323521417200_qiae114-B13","doi-asserted-by":"publisher","first-page":"5868","DOI":"10.1111\/jcmm.14529","article-title":"Toll-like receptor 4: a promising therapeutic target for pneumonia caused by gram-negative bacteria","volume":"23","author":"Ding","year":"2019","journal-title":"J Cell Mol Med"},{"issue":"1","key":"2024110323521417200_qiae114-B14","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1128\/IAI.69.1.518-528.2001","article-title":"Dendritic cells phagocytose and are activated by Treponema pallidum","volume":"69","author":"Bouis","year":"2001","journal-title":"Infect Immun"},{"issue":"5","key":"2024110323521417200_qiae114-B15","doi-asserted-by":"publisher","first-page":"e12526","DOI":"10.1111\/xen.12526","article-title":"A potential role of TLR2 in xenograft rejection of porcine iliac endothelial cells: an in vitro study","volume":"26","author":"Chen","year":"2019","journal-title":"Xenotransplantation"},{"key":"2024110323521417200_qiae114-B16","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/j.bbi.2019.02.004","article-title":"Choroid plexus transcriptome and ultrastructure analysis reveals a TLR2-specific chemotaxis signature and cytoskeleton remodeling in leukocyte trafficking","volume":"79","author":"Mottahedin","year":"2019","journal-title":"Brain Behav Immun"},{"issue":"12","key":"2024110323521417200_qiae114-B17","doi-asserted-by":"publisher","first-page":"4805","DOI":"10.1007\/s00253-021-11380-1","article-title":"Integrated signaling system under endoplasmic reticulum stress in eukaryotic microorganisms","volume":"105","author":"Cao","year":"2021","journal-title":"Appl Microbiol Biotechnol"},{"issue":"11","key":"2024110323521417200_qiae114-B18","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1038\/s41419-021-04318-y","article-title":"PERK signaling through C\/EBP\u03b4 contributes to ER stress-induced expression of immunomodulatory and tumor promoting chemokines by cancer cells","volume":"12","author":"Sheshadri","year":"2021","journal-title":"Cell Death Dis"},{"key":"2024110323521417200_qiae114-B19","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.jss.2018.05.060","article-title":"Hepatic topographical changes of endoplasmic reticulum stress and unfolded protein response signaling after hemorrhagic shock and reperfusion","volume":"231","author":"Wolpert","year":"2018","journal-title":"J Surg Res"},{"issue":"22","key":"2024110323521417200_qiae114-B20","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1093\/eurheartj\/ehv044","article-title":"TLR2 and neutrophils potentiate endothelial stress, apoptosis and detachment: implications for superficial erosion","volume":"36","author":"Quillard","year":"2015","journal-title":"Eur Heart J"},{"issue":"1","key":"2024110323521417200_qiae114-B21","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1007\/s00253-020-11018-8","article-title":"Recombinant Treponema pallidum protein Tp0768 promotes proinflammatory cytokine secretion of macrophages through ER stress and ROS\/NF-\u03baB pathway","volume":"105","author":"Li","year":"2021","journal-title":"Appl Microbiol Biotechnol"},{"issue":"1","key":"2024110323521417200_qiae114-B22","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.smim.2006.12.004","article-title":"TLR signaling","volume":"19","author":"Kawai","year":"2007","journal-title":"Semin Immunol"},{"issue":"5428","key":"2024110323521417200_qiae114-B23","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1126\/science.285.5428.732","article-title":"Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors","volume":"285","author":"Brightbill","year":"1999","journal-title":"Science"},{"issue":"47","key":"2024110323521417200_qiae114-B24","doi-asserted-by":"publisher","first-page":"33419","DOI":"10.1074\/jbc.274.47.33419","article-title":"Toll-like receptor 2 functions as a pattern recognition receptor for diverse bacterial products","volume":"274","author":"Lien","year":"1999","journal-title":"J Biol Chem"}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jleukbio\/advance-article-pdf\/doi\/10.1093\/jleuko\/qiae114\/58466506\/qiae114.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/116\/5\/1045\/60213394\/qiae114.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/116\/5\/1045\/60213394\/qiae114.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,3]],"date-time":"2024-11-03T23:52:29Z","timestamp":1730677949000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/116\/5\/1045\/7674238"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,15]]},"references-count":24,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5,15]]},"published-print":{"date-parts":[[2024,11,4]]}},"URL":"https:\/\/doi.org\/10.1093\/jleuko\/qiae114","relation":{},"ISSN":["1938-3673"],"issn-type":[{"value":"1938-3673","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,11]]},"published":{"date-parts":[[2024,5,15]]}}}