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Nuclear factor-kappa β regulates Notch signaling in production of proinflammatory cytokines and nitric oxide in murine BV-2 microglial cells.
Neuroscience 2011; 192:140-54N

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.

Authors+Show Affiliations

Department of Anatomy, Block MD 10, 4 Medical Drive, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21729740

Citation

Cao, Q, et al. "Nuclear Factor-kappa Β Regulates Notch Signaling in Production of Proinflammatory Cytokines and Nitric Oxide in Murine BV-2 Microglial Cells." Neuroscience, vol. 192, 2011, pp. 140-54.
Cao Q, Kaur C, Wu CY, et al. Nuclear factor-kappa β regulates Notch signaling in production of proinflammatory cytokines and nitric oxide in murine BV-2 microglial cells. Neuroscience. 2011;192:140-54.
Cao, Q., Kaur, C., Wu, C. Y., Lu, J., & Ling, E. A. (2011). Nuclear factor-kappa β regulates Notch signaling in production of proinflammatory cytokines and nitric oxide in murine BV-2 microglial cells. Neuroscience, 192, pp. 140-54. doi:10.1016/j.neuroscience.2011.06.060.
Cao Q, et al. Nuclear Factor-kappa Β Regulates Notch Signaling in Production of Proinflammatory Cytokines and Nitric Oxide in Murine BV-2 Microglial Cells. Neuroscience. 2011 Sep 29;192:140-54. PubMed PMID: 21729740.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nuclear factor-kappa β regulates Notch signaling in production of proinflammatory cytokines and nitric oxide in murine BV-2 microglial cells. AU - Cao,Q, AU - Kaur,C, AU - Wu,C-Y, AU - Lu,J, AU - Ling,E-A, Y1 - 2011/06/26/ PY - 2011/05/18/received PY - 2011/06/21/revised PY - 2011/06/21/accepted PY - 2011/7/7/entrez PY - 2011/7/7/pubmed PY - 2012/1/19/medline SP - 140 EP - 54 JF - Neuroscience JO - Neuroscience VL - 192 N2 - 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. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/21729740/Nuclear_factor_kappa_β_regulates_Notch_signaling_in_production_of_proinflammatory_cytokines_and_nitric_oxide_in_murine_BV_2_microglial_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(11)00749-4 DB - PRIME DP - Unbound Medicine ER -