当前位置： SCI文献检索 > NEUROSCIENCE期刊下所有文献 > Nuclear factor-kappa β regulates Notch signaling in production of proinflammatory cytokines and nitric oxide in murine BV-2 microglial cells.

Nuclear factor-kappa β regulates Notch signaling in production of proinflammatory cytokines and nitric oxide in murine BV-2 microglial cells.

Abstract：

:Microglial cells exhibit Notch-1 signaling expression which is enhanced upon activation. We reported previously that enhanced Notch-1 expression in activated microglia modulates production of proinflammatory cytokines and nitric oxide (NO). Furthermore, Notch-1 modulates transcription factor nuclear factor-kappa B (NF-κB). This study was aimed to investigate if NF-κB reciprocally modulates Notch signaling in BV-2 cells. In this connection, the cells were pretreated with caffeic acid phenethyl ester (Cape) followed by stimulating the cells with lipopolysaccharide (LPS). Cape+LPS treatment resulted in reduced translocation of NF-κB into the nucleus. Concomitantly, NF-κB DNA binding activity and the mRNA and protein expression levels of NF-κB/p65, Notch-1, intracellular domain of Notch-1 receptor (NICD), Hes-1, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and inducible nitric oxide synthase (iNOS) along with nitrite level were significantly reduced. Additionally, flow cytometry analysis showed a decrease in expression levels of NF-κB/p65, Notch-1, NICD but an increase in that of signal transducers and activators of transcription 3 (Stat3). Furthermore, nuclear Hes-1, phosphorylated Stat3 (p-Stat3) and recombination signal-binding protein 1 for J-Kappa (RBP-JK) expression levels were significantly suppressed. The present results suggest that Cape inhibits NF-κB activation through suppressing its interaction with DNA. Cape-induced reduction of Hes-1 may be attributed to decreased interaction between NICD and RBP-JK whose levels were reduced concurrently. Hes-1 reduction may lead to decreased production of inflammatory cytokines and NO. It is concluded that NF-κB can modulate Notch-1 signaling. Both pathways operate synergistically for production of proinflammatory cytokines and NO in activated microglia.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Cao Q,Kaur C,Wu CY,Lu J,Ling EA

doi

10.1016/j.neuroscience.2011.06.060

subject

Has Abstract

pub_date

2011-09-29 00:00:00

pages

140-54

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(11)00749-4

journal_volume

192

pub_type

杂志文章

相关文献

NEUROSCIENCE文献大全