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NF?B is an unexpected major mediator of interleukin-15 signaling in cerebral endothelia.

ABSTRACT: Interleukin (IL)-15 and its receptors are induced by tumor necrosis factor ? (TNF) in the cerebral endothelial cells composing the blood-brain barrier, but it is not yet clear how IL-15 modulates endothelial function. Contrary to the known induction of JAK/STAT3 signaling, here we found that nuclear factor (NF)- ?B is mainly responsible for IL-15 actions on primary brain microvessel endothelial cells and cerebral endothelial cell lines. IL-15-induced transactivation of an NF?B luciferase reporter resulted in phosphorylation and degradation of the inhibitory subunit I?B that was followed by phosphorylation and nuclear translocation of the p65 subunit of NF?B. An I?B kinase inhibitor Bay 11-7082 only partially inhibited IL-15-induced NF?B luciferase activity. The effect of IL-15 was mediated by its specific receptor IL-15R?, since endothelia from IL-15R? knockout mice showed delayed nuclear translocation of p65, whereas those from knockout mice lacking a co-receptor IL-2R? did not show such changes. At the mRNA level, IL-15 and TNF showed similar effects in decreasing the tight junction protein claudin-2 and increasing the p65 subunit of NF?B but exerted different regulation on caveolin-1 and vimentin. Taken together, NF?B is a major signal transducer by which IL-15 affects cellular permeability, endocytosis, and intracellular trafficking at the level of the blood-brain barrier.

SUBMITTER: Stone KP

PROVIDER: S-EPMC3709181 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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NFĸB is an unexpected major mediator of interleukin-15 signaling in cerebral endothelia.

Stone Kirsten P KP Kastin Abba J AJ Pan Weihong W

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 20110816 1

Interleukin (IL)-15 and its receptors are induced by tumor necrosis factor α (TNF) in the cerebral endothelial cells composing the blood-brain barrier, but it is not yet clear how IL-15 modulates endothelial function. Contrary to the known induction of JAK/STAT3 signaling, here we found that nuclear factor (NF)- κB is mainly responsible for IL-15 actions on primary brain microvessel endothelial cells and cerebral endothelial cell lines. IL-15-induced transactivation of an NFκB luciferase reporte ...[more]

PMID: 21865854

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NF?B is an unexpected major mediator of interleukin-15 signaling in cerebral endothelia.

Publications

NFĸB is an unexpected major mediator of interleukin-15 signaling in cerebral endothelia.

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