title: Transitory loss of glia and the subsequent modulation in inflammatory cytokines/chemokines regulate paracellular claudin-5 expression in endothelial cells.
abstract: Signaling mechanisms involved in regulating blood-brain barrier (BBB) integrity during central nervous system (CNS) inflammation remain unclear. We show that an imbalance between pro-/anti-inflammatory cytokines/chemokines alters claudin-5 expression. In vivo, gliotoxin-induced changes in glial populations and an imbalance between pro-/anti-inflammatory cytokine/chemokine expression occurred as BBB integrity was compromised. The balance was restored as BBB integrity was re-established. In vitro, TNF-α, IL-6, and MCP-1 induced paracellular claudin-5 expression loss. TNF-α- and IL-6- effects were mediated through the PI3K pathway and IL-10 attenuated TNF-α's effect. This study shows that pro-/anti-inflammatory modulators play a critical role in BBB integrity during CNS inflammation.
authors.affiliation: Westbrook College of Health Professions, University of New England, Biddeford, ME 04005, USA. Electronic address: rcamire@une.edu.
authors.forename: Ryan B
authors.initials: RB
authors.lastname: Camire
authors.affiliation: Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, ME 04005, USA; Center for Excellence in the Neurosciences, University of New England, Biddeford, ME 04005, USA. Electronic address: hbeaulac@une.edu.
authors.forename: Holly J
authors.initials: HJ
authors.lastname: Beaulac
authors.affiliation: Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, ME 04005, USA; Center for Excellence in the Neurosciences, University of New England, Biddeford, ME 04005, USA. Electronic address: clwillis@outlook.com.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Willis
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D002461:Cell Line, Transformed; D002629:Chemosterilants / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D062507:Claudin-5 / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007245:Inferior Colliculi / Q000166:cytology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009025:Morpholines / Q000494:pharmacology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D000517:alpha-Chlorohydrin / Q000494:pharmacology
chemical_list: D039481:CD11b Antigen; D002629:Chemosterilants; D002867:Chromones; D062507:Claudin-5; D016207:Cytokines; D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; D009025:Morpholines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D000517:alpha-Chlorohydrin
keywords: Astrocytes; Blood–brain barrier; Chemokine; Claudin-5; Cytokine; Microglia