Journal
JOURNAL OF NEUROCHEMISTRY
Volume 78, Issue 1, Pages 155-162Publisher
WILEY
DOI: 10.1046/j.1471-4159.2001.00399.x
Keywords
astrocytes; NF-kappa B; occludin; tight junctions; TNF
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Tight junctions form the diffusion barrier of brain microcapillary endothelial cells and support cell polarity. Also astrocytes express tight junction components such as occludin, claudin-1, ZO-1 and ZO-2, but do not establish a permeability barrier. However, little is known about the function and regulation of these molecules in astrocytes. We studied the impact of tumour necrosis factor (TNF) on occludin and ZO-1 expression in astrocytes. TNF decreased occludin, but not ZO-1 expression, in brain microcapillary endothelial cells, as well as in epithelial cells. occludin expression was not influenced by TNF. Removal of TNF from astrocytes restored the basal level of occludin. Down-regulation was inhibited by caffeic acid phenethyl ester, a specific inhibitor of nuclear factor-kappaB (NF-kappaB) activation. Exposure of astrocytes isolated from mice deficient in either TNF type-1 receptor (TNFR1), TNF type-2 receptor (TNFR2), or both, respectively, revealed that downregulation was mediated entirely by TNFR1. ZO-1, which can interact with occludin, was found to cc-precipitate connexin43, but not occludin, These findings demonstrate that TNF selectively down-regulates occludin in astrocytes, but not in cells forming established tight junctions, through TNFR1 and suggest that NF-kappaB is involved as a negative regulator.
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