{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:21:51Z","timestamp":1760242911863,"version":"build-2065373602"},"reference-count":58,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2016,10,13]],"date-time":"2016-10-13T00:00:00Z","timestamp":1476316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB629 TP B02","EXC 1003 - CIM"],"award-info":[{"award-number":["SFB629 TP B02","EXC 1003 - CIM"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Pertussis toxin (PTx), the major virulence factor of the whooping cough-causing bacterial pathogen Bordetella pertussis, permeabilizes the blood\u2013brain barrier (BBB) in vitro and in vivo. Breaking barriers might promote translocation of meningitis-causing bacteria across the BBB, thereby facilitating infection. PTx activates several host cell signaling pathways exploited by the neonatal meningitis-causing Escherichia coli K1-RS218 for invasion and translocation across the BBB. Here, we investigated whether PTx and E. coli K1-RS218 exert similar effects on MAPK p38, NF-\u03baB activation and transcription of downstream targets in human cerebral endothelial TY10 cells using qRT-PCR, Western blotting, and ELISA in combination with specific inhibitors. PTx and E. coli K1-RS218 activate MAPK p38, but only E. coli K1-RS218 activates the NF-\u03baB pathway. mRNA and protein levels of p38 and NF-\u03baB downstream targets including IL-6, IL-8, CxCL-1, CxCL-2 and ICAM-1 were increased. The p38 specific inhibitor SB203590 blocked PTx-enhanced activity, whereas E. coli K1-RS218\u2019s effects were inhibited by the NF-\u03baB inhibitor Bay 11-7082. Further, we found that PTx enhances the adherence of human monocytic THP-1 cells to human cerebral endothelial TY10 cells, thereby contributing to enhanced translocation. These modulations of host cell signaling pathways by PTx and meningitis-causing E. coli support their contributions to pathogen and monocytic THP-1 cells translocation across the BBB.<\/jats:p>","DOI":"10.3390\/toxins8100291","type":"journal-article","created":{"date-parts":[[2016,10,13]],"date-time":"2016-10-13T10:33:10Z","timestamp":1476354790000},"page":"291","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pertussis Toxin Exploits Host Cell Signaling Pathways Induced by Meningitis-Causing E. coli K1-RS218 and Enhances Adherence of Monocytic THP-1 Cells to Human Cerebral Endothelial Cells"],"prefix":"10.3390","volume":"8","author":[{"given":"Laura","family":"Starost","sequence":"first","affiliation":[{"name":"Institute of Infectiology, Center of Molecular Biology of Inflammation, Westf\u00e4lische Wilhelms-Universit\u00e4t M\u00fcnster, M\u00fcnster D-48149, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sascha","family":"Karassek","sequence":"additional","affiliation":[{"name":"Institute of Infectiology, Center of Molecular Biology of Inflammation, Westf\u00e4lische Wilhelms-Universit\u00e4t M\u00fcnster, M\u00fcnster D-48149, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuteru","family":"Sano","sequence":"additional","affiliation":[{"name":"Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Yamaguchi, Ube City 755-8505, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Kanda","sequence":"additional","affiliation":[{"name":"Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Yamaguchi, Ube City 755-8505, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwang","family":"Kim","sequence":"additional","affiliation":[{"name":"Pediatric Infectious Diseases Division, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Dobrindt","sequence":"additional","affiliation":[{"name":"Institute of Hygiene, Microbial Genome Plasticity\u2014Molecular Infection Biology, Westf\u00e4lische Wilhelms-Universit\u00e4t M\u00fcnster, M\u00fcnster D-48149, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"R\u00fcter","sequence":"additional","affiliation":[{"name":"Institute of Infectiology, Center of Molecular Biology of Inflammation, Westf\u00e4lische Wilhelms-Universit\u00e4t M\u00fcnster, M\u00fcnster D-48149, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Institute of Infectiology, Center of Molecular Biology of Inflammation, Westf\u00e4lische Wilhelms-Universit\u00e4t M\u00fcnster, M\u00fcnster D-48149, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2016,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1093\/clinids\/1.3.401","article-title":"Pertussis toxin: The cause of the harmful effects and prolonged immunity of whooping cough. 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