The intracellular mechanism of NF-κB activation involved in iNOS and chemokine induction in C6 glioma cells
-
- Nomura Yasuyuki
- Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University
-
- Uehara Takashi
- Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University
-
- Nishiya Tadashi
- Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University
Bibliographic Information
- Other Title
-
- グリア細胞のiNos,ケモカイン発現に関わるNF-κB系活性制御と薬物作用
- グリア サイボウ ノ iNOS ケモカイン ハツゲン ニ カカワル NF カッパBケイ カッセイ セイギョ ト ヤクブツ サヨウ
Search this article
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-1β-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.
Journal
-
- Folia Pharmacologica Japonica
-
Folia Pharmacologica Japonica 114 (supplement), 92-95, 1999
The Japanese Pharmacological Society
- Tweet
Details 詳細情報について
-
- CRID
- 1390282679247568000
-
- NII Article ID
- 130000754524
-
- NII Book ID
- AN00198335
-
- ISSN
- 13478397
- 00155691
-
- NDL BIB ID
- 4910386
-
- Text Lang
- ja
-
- Data Source
-
- JaLC
- NDL
- Crossref
- CiNii Articles
-
- Abstract License Flag
- Disallowed