title: Endothelial Japanese encephalitis virus infection enhances migration and adhesion of leukocytes to brain microvascular endothelia via MEK-dependent expression of ICAM1 and the CINC and RANTES chemokines.
abstract: Currently, the underlying mechanisms and the specific cell types associated with Japanese encephalitis-associated leukocyte trafficking are not understood. Brain microvascular endothelial cells represent a functional barrier and could play key roles in leukocyte central nervous system trafficking. We found that cultured brain microvascular endothelial cells were susceptible to Japanese encephalitis virus (JEV) infection with limited amplification. This type of JEV infection had negligible effects on cell viability and barrier integrity. Instead, JEV-infected endothelial cells attracted more leukocytes adhesion onto surfaces and the supernatants promoted chemotaxis of leukocytes. Infection with JEV was found to elicit the elevated production of intercellular adhesion molecule-1, cytokine-induced neutrophil chemoattractant-1, and regulated-upon-activation normal T-cell expressed and secreted, contributing to the aforementioned leukocyte adhesion and chemotaxis. We further demonstrated that extracellular signal-regulated kinase was a key upstream regulator which stimulated extensive endothelial gene induction by up-regulating cytosolic phospholipase A₂, NF-κB, and cAMP response element-binding protein via signals involving phosphorylation. These data suggest that JEV 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-disrupting mechanisms contributing to Japanese encephalitis and associated neuroinflammation.
authors: Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
authors: Ching-Yi
authors: CY
authors: Lai
authors: Yen-Chuan
authors: YC
authors: Ou
authors: Cheng-Yi
authors: CY
authors: Chang
authors: Hung-Chuan
authors: HC
authors: Pan
authors: Chen-Jung
authors: CJ
authors: Chang
authors: Su-Lan
authors: SL
authors: Liao
authors: Hong-Lin
authors: HL
authors: Su
authors: Chun-Jung
authors: CJ
authors: Chen
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D018925:Chemokines / Q000096:biosynthesis; D019743:Chemokines, CXC / Q000096:biosynthesis*; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D006224:Cricetinae; D004664:Encephalitis Virus, Japanese; D004672:Encephalitis, Japanese / Q000276:immunology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism; D005260:Female; D015967:Gene Expression Regulation, Viral; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear; D008297:Male; D008833:Microcirculation / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases; D017207:Rats, Sprague-Dawley
chemical_list: D018946:Chemokine CCL5; D018925:Chemokines; D019743:Chemokines, CXC; D018799:Intercellular Adhesion Molecule-1; D020928:Mitogen-Activated Protein Kinases