[PDF][PDF] Reciprocal regulation of the junctional proteins claudin-1 and connexin43 by interleukin-1β in primary human fetal astrocytes

HS Duffy, GR John, SC Lee, CF Brosnan… - The Journal of …, 2000 - Soc Neuroscience
HS Duffy, GR John, SC Lee, CF Brosnan, DC Spray
The Journal of Neuroscience, 2000Soc Neuroscience
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 …
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-1฿ (IL-1฿) 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-1฿-treated astrocytes, whereas freezefracture replicas showed strand-like arrays of intramembranous particles in treated cells resembling rudimentary TJ assemblies. We conclude that in human astrocytes, IL-1฿ 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-1฿ expression fundamentally alters astrocyte-to-astrocyte connectivity.
Soc Neuroscience