Journal of Neuroimmunology 2015-07-15

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

Index: J. Neuroimmunol. 284 , 57-66, (2015)

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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. Copyright © 2015 Elsevier B.V. All rights reserved.