Transitory loss of glia and the subsequent modulation in inflammatory cytokines/chemokines regulate paracellular claudin-5 expression in endothelial cells

Ryan B Camire; Holly J Beaulac; Colin L Willis

doi:10.1016/j.jneuroim.2015.05.008

Transitory loss of glia and the subsequent modulation in inflammatory cytokines/chemokines regulate paracellular claudin-5 expression in endothelial cells

J Neuroimmunol. 2015 Jul 15:284:57-66. doi: 10.1016/j.jneuroim.2015.05.008. Epub 2015 May 13.

Authors

Ryan B Camire¹, Holly J Beaulac², Colin L Willis³

Affiliations

¹ Westbrook College of Health Professions, University of New England, Biddeford, ME 04005, USA. Electronic address: rcamire@une.edu.
² 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.
³ 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.

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.

Keywords: Astrocytes; Blood–brain barrier; Chemokine; Claudin-5; Cytokine; Microglia.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD11b Antigen / metabolism
Cell Line, Transformed
Chemosterilants / pharmacology
Chromones / pharmacology
Claudin-5 / metabolism*
Cytokines / metabolism*
Cytokines / pharmacology
Dose-Response Relationship, Drug
Drug Interactions
Endothelial Cells / drug effects
Endothelial Cells / metabolism*
Enzyme Inhibitors / pharmacology
Gene Expression Regulation / drug effects
Glial Fibrillary Acidic Protein / metabolism
Inferior Colliculi / cytology*
Male
Mice
Mice, Inbred BALB C
Morpholines / pharmacology
Neuroglia / drug effects
Neuroglia / metabolism*
Rats
Rats, Inbred F344
Time Factors
alpha-Chlorohydrin / pharmacology

Substances

CD11b Antigen
Chemosterilants
Chromones
Claudin-5
Cytokines
Enzyme Inhibitors
Glial Fibrillary Acidic Protein
Morpholines
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
alpha-Chlorohydrin

Abstract

Publication types

MeSH terms

Substances

Grants and funding