Reciprocal regulation of the junctional proteins claudin-1 and connexin43 by interleukin-1beta in primary human fetal astrocytes.

H. S. Duffy, G. R. John, S. C. Lee, C. F. Brosnan, David C. Spray

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Vertebrate tissues use multiple junctional types to establish and maintain tissue architecture, including gap junctions for cytoplasmic connectivity and tight junctions (TJs) for paracellular and/or cell polarity barriers. The integral membrane proteins of gap junctions are connexins, whereas TJs are a complex between occludin and members of a recently characterized multigene family, the claudins. In normal brain, astrocytes are coupled by gap junctions composed primarily of connexin43 (Cx43), whereas TJs have not been detected in these cells. We now show that treatment of primary human astrocytes with the cytokine interleukin-1beta (IL-1beta) causes rapid induction of claudin-1, with an expression pattern reciprocal to loss of Cx43. Treatment also led to protracted downregulation of occludin but no change in expression of zonula occludens proteins ZO-1 and -2. Immunofluorescence staining localized claudin-1 to cell membranes in IL-1beta-treated astrocytes, whereas freeze-fracture replicas showed strand-like arrays of intramembranous particles in treated cells resembling rudimentary TJ assemblies. We conclude that in human astrocytes, IL-1beta regulates expression of the claudin multigene family and that gap and tight junction proteins are inversely regulated by this proinflammatory cytokine. We suggest that in pathological conditions of the human CNS, elevated IL-1beta expression fundamentally alters astrocyte-to-astrocyte connectivity.

Original languageEnglish (US)
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Volume20
Issue number23
StatePublished - 2000

Fingerprint

Claudin-1
Connexin 43
Interleukin-1beta
Astrocytes
Tight Junctions
Gap Junctions
Occludin
Proteins
Connexins
Multigene Family
Zonula Occludens-1 Protein
Claudins
Cytokines
Tight Junction Proteins
Cell Polarity
Fluorescent Antibody Technique
Vertebrates
Membrane Proteins
Down-Regulation
Cell Membrane

Cite this

@article{e760860cb1814aafad3fb98a20396a66,
title = "Reciprocal regulation of the junctional proteins claudin-1 and connexin43 by interleukin-1beta in primary human fetal astrocytes.",
abstract = "Vertebrate tissues use multiple junctional types to establish and maintain tissue architecture, including gap junctions for cytoplasmic connectivity and tight junctions (TJs) for paracellular and/or cell polarity barriers. The integral membrane proteins of gap junctions are connexins, whereas TJs are a complex between occludin and members of a recently characterized multigene family, the claudins. In normal brain, astrocytes are coupled by gap junctions composed primarily of connexin43 (Cx43), whereas TJs have not been detected in these cells. We now show that treatment of primary human astrocytes with the cytokine interleukin-1beta (IL-1beta) causes rapid induction of claudin-1, with an expression pattern reciprocal to loss of Cx43. Treatment also led to protracted downregulation of occludin but no change in expression of zonula occludens proteins ZO-1 and -2. Immunofluorescence staining localized claudin-1 to cell membranes in IL-1beta-treated astrocytes, whereas freeze-fracture replicas showed strand-like arrays of intramembranous particles in treated cells resembling rudimentary TJ assemblies. We conclude that in human astrocytes, IL-1beta regulates expression of the claudin multigene family and that gap and tight junction proteins are inversely regulated by this proinflammatory cytokine. We suggest that in pathological conditions of the human CNS, elevated IL-1beta expression fundamentally alters astrocyte-to-astrocyte connectivity.",
author = "Duffy, {H. S.} and John, {G. R.} and Lee, {S. C.} and Brosnan, {C. F.} and Spray, {David C.}",
year = "2000",
language = "English (US)",
volume = "20",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "23",

}

TY - JOUR

T1 - Reciprocal regulation of the junctional proteins claudin-1 and connexin43 by interleukin-1beta in primary human fetal astrocytes.

AU - Duffy, H. S.

AU - John, G. R.

AU - Lee, S. C.

AU - Brosnan, C. F.

AU - Spray, David C.

PY - 2000

Y1 - 2000

N2 - Vertebrate tissues use multiple junctional types to establish and maintain tissue architecture, including gap junctions for cytoplasmic connectivity and tight junctions (TJs) for paracellular and/or cell polarity barriers. The integral membrane proteins of gap junctions are connexins, whereas TJs are a complex between occludin and members of a recently characterized multigene family, the claudins. In normal brain, astrocytes are coupled by gap junctions composed primarily of connexin43 (Cx43), whereas TJs have not been detected in these cells. We now show that treatment of primary human astrocytes with the cytokine interleukin-1beta (IL-1beta) causes rapid induction of claudin-1, with an expression pattern reciprocal to loss of Cx43. Treatment also led to protracted downregulation of occludin but no change in expression of zonula occludens proteins ZO-1 and -2. Immunofluorescence staining localized claudin-1 to cell membranes in IL-1beta-treated astrocytes, whereas freeze-fracture replicas showed strand-like arrays of intramembranous particles in treated cells resembling rudimentary TJ assemblies. We conclude that in human astrocytes, IL-1beta regulates expression of the claudin multigene family and that gap and tight junction proteins are inversely regulated by this proinflammatory cytokine. We suggest that in pathological conditions of the human CNS, elevated IL-1beta expression fundamentally alters astrocyte-to-astrocyte connectivity.

AB - Vertebrate tissues use multiple junctional types to establish and maintain tissue architecture, including gap junctions for cytoplasmic connectivity and tight junctions (TJs) for paracellular and/or cell polarity barriers. The integral membrane proteins of gap junctions are connexins, whereas TJs are a complex between occludin and members of a recently characterized multigene family, the claudins. In normal brain, astrocytes are coupled by gap junctions composed primarily of connexin43 (Cx43), whereas TJs have not been detected in these cells. We now show that treatment of primary human astrocytes with the cytokine interleukin-1beta (IL-1beta) causes rapid induction of claudin-1, with an expression pattern reciprocal to loss of Cx43. Treatment also led to protracted downregulation of occludin but no change in expression of zonula occludens proteins ZO-1 and -2. Immunofluorescence staining localized claudin-1 to cell membranes in IL-1beta-treated astrocytes, whereas freeze-fracture replicas showed strand-like arrays of intramembranous particles in treated cells resembling rudimentary TJ assemblies. We conclude that in human astrocytes, IL-1beta regulates expression of the claudin multigene family and that gap and tight junction proteins are inversely regulated by this proinflammatory cytokine. We suggest that in pathological conditions of the human CNS, elevated IL-1beta expression fundamentally alters astrocyte-to-astrocyte connectivity.

UR - http://www.scopus.com/inward/record.url?scp=0034576040&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034576040&partnerID=8YFLogxK

M3 - Article

C2 - 11090614

AN - SCOPUS:0034576040

VL - 20

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 23

ER -