The intracellular mechanism of NF-κB activation involved in iNOS and chemokine induction in C6 glioma cells

Y. Nomura, Takashi Uehara, T. Nishiya

Research output: Contribution to journalArticle

Abstract

To elucidate the intracellular mechanism of NF-κB activation, we performed the involvement of IκBα of NF-κB in the expression of inducible NO synthase (iNOS) and chemokine (CINC) following pretreatment with bacterial endotoxin (LPS) or IL-1β, respectively, using rat C6 glioma cells. We found that herbimycin A, a tyrosine protein kinase inhibitor, blocked: 1) LPS/IFNγ-induced iNOS expression, 2) LPS-induced intranuclear translocation of activated NF-κB (p50 · p65) and 3) IFNγ-induced autophosphorylation and activation of Jak 2 and Stat 1 as well as intranuclear translocation of phosphorylated Stat 1. Furthermore, transfection of a dominant negative form of IκBα(SS → AA) suppressed LPS/IFNγ-induced iNOS expression, suggesting that NF-κB, in particular, IκBα molecules could play important roles in the iNOS expression. We also found in IL-Iβ-induced CINC expression using cultured C6 glioma cells, the transient translocation of NF-κB in response to IL- 1β is partly dependent on transient proteasome activation. Thus we suggest that the formation of heterodimer p50·p65 from inactive trimer p50·p65·IκBα, particularly, proteolytic degradation and dissociation of IκBα from p50·p65 are a critical phase in NF-κB activation during LPS- induced iNOS and IL- 1β induced CINC expression in astroglial cells.

Original languageEnglish
JournalFolia Pharmacologica Japonica
Volume114
Issue numberSUPPL. 1
Publication statusPublished - 1999
Externally publishedYes

Fingerprint

Chemokines
Nitric Oxide Synthase
Glioma
Interleukin-1
Proteasome Endopeptidase Complex
Protein Kinase Inhibitors
Endotoxins
Protein-Tyrosine Kinases
Transfection

Keywords

  • Chemokine
  • Glia
  • IκBα
  • INOS
  • NF-κB

ASJC Scopus subject areas

  • Pharmacology

Cite this

The intracellular mechanism of NF-κB activation involved in iNOS and chemokine induction in C6 glioma cells. / Nomura, Y.; Uehara, Takashi; Nishiya, T.

In: Folia Pharmacologica Japonica, Vol. 114, No. SUPPL. 1, 1999.

Research output: Contribution to journalArticle

@article{28307ebb1996447baa845295bf6be22e,
title = "The intracellular mechanism of NF-κB activation involved in iNOS and chemokine induction in C6 glioma cells",
abstract = "To elucidate the intracellular mechanism of NF-κB activation, we performed the involvement of IκBα of NF-κB in the expression of inducible NO synthase (iNOS) and chemokine (CINC) following pretreatment with bacterial endotoxin (LPS) or IL-1β, respectively, using rat C6 glioma cells. We found that herbimycin A, a tyrosine protein kinase inhibitor, blocked: 1) LPS/IFNγ-induced iNOS expression, 2) LPS-induced intranuclear translocation of activated NF-κB (p50 · p65) and 3) IFNγ-induced autophosphorylation and activation of Jak 2 and Stat 1 as well as intranuclear translocation of phosphorylated Stat 1. Furthermore, transfection of a dominant negative form of IκBα(SS → AA) suppressed LPS/IFNγ-induced iNOS expression, suggesting that NF-κB, in particular, IκBα molecules could play important roles in the iNOS expression. We also found in IL-Iβ-induced CINC expression using cultured C6 glioma cells, the transient translocation of NF-κB in response to IL- 1β is partly dependent on transient proteasome activation. Thus we suggest that the formation of heterodimer p50·p65 from inactive trimer p50·p65·IκBα, particularly, proteolytic degradation and dissociation of IκBα from p50·p65 are a critical phase in NF-κB activation during LPS- induced iNOS and IL- 1β induced CINC expression in astroglial cells.",
keywords = "Chemokine, Glia, IκBα, INOS, NF-κB",
author = "Y. Nomura and Takashi Uehara and T. Nishiya",
year = "1999",
language = "English",
volume = "114",
journal = "Folia Pharmacologica Japonica",
issn = "0015-5691",
publisher = "Japanese Pharmacological Society",
number = "SUPPL. 1",

}

TY - JOUR

T1 - The intracellular mechanism of NF-κB activation involved in iNOS and chemokine induction in C6 glioma cells

AU - Nomura, Y.

AU - Uehara, Takashi

AU - Nishiya, T.

PY - 1999

Y1 - 1999

N2 - To elucidate the intracellular mechanism of NF-κB activation, we performed the involvement of IκBα of NF-κB in the expression of inducible NO synthase (iNOS) and chemokine (CINC) following pretreatment with bacterial endotoxin (LPS) or IL-1β, respectively, using rat C6 glioma cells. We found that herbimycin A, a tyrosine protein kinase inhibitor, blocked: 1) LPS/IFNγ-induced iNOS expression, 2) LPS-induced intranuclear translocation of activated NF-κB (p50 · p65) and 3) IFNγ-induced autophosphorylation and activation of Jak 2 and Stat 1 as well as intranuclear translocation of phosphorylated Stat 1. Furthermore, transfection of a dominant negative form of IκBα(SS → AA) suppressed LPS/IFNγ-induced iNOS expression, suggesting that NF-κB, in particular, IκBα molecules could play important roles in the iNOS expression. We also found in IL-Iβ-induced CINC expression using cultured C6 glioma cells, the transient translocation of NF-κB in response to IL- 1β is partly dependent on transient proteasome activation. Thus we suggest that the formation of heterodimer p50·p65 from inactive trimer p50·p65·IκBα, particularly, proteolytic degradation and dissociation of IκBα from p50·p65 are a critical phase in NF-κB activation during LPS- induced iNOS and IL- 1β induced CINC expression in astroglial cells.

AB - To elucidate the intracellular mechanism of NF-κB activation, we performed the involvement of IκBα of NF-κB in the expression of inducible NO synthase (iNOS) and chemokine (CINC) following pretreatment with bacterial endotoxin (LPS) or IL-1β, respectively, using rat C6 glioma cells. We found that herbimycin A, a tyrosine protein kinase inhibitor, blocked: 1) LPS/IFNγ-induced iNOS expression, 2) LPS-induced intranuclear translocation of activated NF-κB (p50 · p65) and 3) IFNγ-induced autophosphorylation and activation of Jak 2 and Stat 1 as well as intranuclear translocation of phosphorylated Stat 1. Furthermore, transfection of a dominant negative form of IκBα(SS → AA) suppressed LPS/IFNγ-induced iNOS expression, suggesting that NF-κB, in particular, IκBα molecules could play important roles in the iNOS expression. We also found in IL-Iβ-induced CINC expression using cultured C6 glioma cells, the transient translocation of NF-κB in response to IL- 1β is partly dependent on transient proteasome activation. Thus we suggest that the formation of heterodimer p50·p65 from inactive trimer p50·p65·IκBα, particularly, proteolytic degradation and dissociation of IκBα from p50·p65 are a critical phase in NF-κB activation during LPS- induced iNOS and IL- 1β induced CINC expression in astroglial cells.

KW - Chemokine

KW - Glia

KW - IκBα

KW - INOS

KW - NF-κB

UR - http://www.scopus.com/inward/record.url?scp=0032755031&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032755031&partnerID=8YFLogxK

M3 - Article

VL - 114

JO - Folia Pharmacologica Japonica

JF - Folia Pharmacologica Japonica

SN - 0015-5691

IS - SUPPL. 1

ER -