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We found that cultured brain microvascular endothelial cells were susceptible to Japanese encephalitis virus (<jats:styled-content style=\"fixed-case\">JEV<\/jats:styled-content>) infection with limited amplification. This type of <jats:styled-content style=\"fixed-case\">JEV<\/jats:styled-content> infection had negligible effects on cell viability and barrier integrity. Instead, <jats:styled-content style=\"fixed-case\">JEV<\/jats:styled-content>\u2010infected endothelial cells attracted more leukocytes adhesion onto surfaces and the supernatants promoted chemotaxis of leukocytes. Infection with <jats:styled-content style=\"fixed-case\">JEV<\/jats:styled-content> was found to elicit the elevated production of intercellular adhesion molecule\u20101, cytokine\u2010induced neutrophil chemoattractant\u20101, and regulated\u2010upon\u2010activation normal <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010cell expressed and secreted, contributing to the aforementioned leukocyte adhesion and chemotaxis. We further demonstrated that extracellular signal\u2010regulated kinase was a key upstream regulator which stimulated extensive endothelial gene induction by up\u2010regulating cytosolic phospholipase A<jats:sub>2<\/jats:sub>, <jats:styled-content style=\"fixed-case\">NF\u2010\u03baB<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content> response element\u2010binding protein via signals involving phosphorylation. These data suggest that <jats:styled-content style=\"fixed-case\">JEV<\/jats:styled-content> infection could activate brain microvascular endothelial cells and modify their characteristics without compromising the barrier integrity, making them favorable for the recruitment and adhesion of circulating leukocytes, thereby together with other unidentified barrier\u2010disrupting mechanisms contributing to Japanese encephalitis and associated neuroinflammation.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2012.07889.x","type":"journal-article","created":{"date-parts":[[2012,7,28]],"date-time":"2012-07-28T14:45:44Z","timestamp":1343486744000},"page":"250-261","source":"Crossref","is-referenced-by-count":55,"title":["Endothelial <scp>J<\/scp>apanese encephalitis virus infection enhances migration and adhesion of leukocytes to brain microvascular endothelia via <scp>MEK<\/scp>\u2010dependent expression of <scp>ICAM<\/scp>1 and the <scp>CINC<\/scp> and <scp>RANTES<\/scp> chemokines"],"prefix":"10.1111","volume":"123","author":[{"given":"Ching\u2010Yi","family":"Lai","sequence":"first","affiliation":[{"name":"Department of Life Sciences National Chung Hsing University Taichung Taiwan"},{"name":"Department of Education and Research Taichung Veterans General Hospital Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen\u2010Chuan","family":"Ou","sequence":"additional","affiliation":[{"name":"Division of Urology Taichung Veterans General Hospital Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng\u2010Yi","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Surgery Fong\u2010Yuan Hospital Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung\u2010Chuan","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Taichung Veterans General Hospital Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen\u2010Jung","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging and Radiological Sciences Central Taiwan University of Sciences and Technology Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su\u2010Lan","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Education and Research Taichung Veterans General Hospital Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2010Lin","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Life Sciences National Chung Hsing University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2010Jung","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Education and Research Taichung Veterans General Hospital Taichung Taiwan"},{"name":"Center for General Education Tunghai University Taichung Taiwan"},{"name":"Institute of Biomedical Sciences National Chung Hsing University Taichung Taiwan"},{"name":"Graduate School of Nursing Hung\u2010Kuang University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,8,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000205"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10762"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.44.100190.003245"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-72-4-859"},{"key":"e_1_2_7_6_1","first-page":"2000","article-title":"Prostaglandin E2 and the protein kinase A pathway mediate arachidonic acid induction of c\u2010fos in human prostate cancer cells","volume":"82","author":"Chen Y.","year":"2000","journal-title":"Br. 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