RRC ID |
49556
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著者 |
Quach HT, Kondo T, Watanabe M, Tamura R, Yajima Y, Sayama S, Ando M, Kataoka T.
|
タイトル |
Eudesmane-Type Sesquiterpene Lactones Inhibit Nuclear Translocation of the Nuclear Factor κB Subunit RelB in Response to a Lymphotoxin β Stimulation.
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ジャーナル |
Biol Pharm Bull
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Abstract |
The transcription factor nuclear factor κB (NF-κB) regulates various biological processes, including inflammatory responses. We previously reported that eudesmane-type sesquiterpene lactones inhibited multiple steps in the canonical NF-κB signaling pathway induced by tumor necrosis factor-α and interleukin-1α. In contrast, the biological activities of eudesmane-type sesquiterpene lactones on the non-canonical NF-κB signaling pathway remain unclear. In the present study, we found that (11S)-2α-bromo-3-oxoeudesmano-12,6α-lactone, designated santonin-related compound 2 (SRC2), inhibited NF-κB luciferase reporter activity induced by lymphotoxin β (LTβ) in human lung carcinoma A549 cells. Although SRC2 did not prevent the processing of the NF-κB subunit p100 induced by LTβ, it inhibited the nuclear translocation of RelB and p52 in response to the LTβ stimulation. In contrast to (-)-dehydroxymethylepoxyquinomicin, SRC2 inhibited the LTβ-induced nuclear translocation of the RelB (C144S) mutant in a manner similar to wild-type RelB. While eudesmane derivatives possessing an α-bromoketone moiety or α,β-unsaturated carbonyl moieties inhibited LTβ-induced NF-κB luciferase reporter activity, eudesmane derivatives possessing an α-bromoketone moiety exhibited stronger inhibitory activity on the LTβ-induced nuclear translocation of RelB than those possessing a single α-methylene-γ-lactone moiety. The results of the present study revealed that SRC2 inhibits the nuclear translocation of RelB in the non-canonical NF-κB signaling pathway induced by LTβ.
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巻・号 |
40(10)
|
ページ |
1669-1677
|
公開日 |
2017-1-1
|
DOI |
10.1248/bpb.b17-00170
|
PMID |
28966239
|
MeSH |
A549 Cells
Cell Nucleus / metabolism
Humans
Lactones / pharmacology*
Lymphotoxin-beta / pharmacology*
NF-kappa B / metabolism*
Protein Transport / drug effects*
Sesquiterpenes, Eudesmane / pharmacology*
|
IF |
1.863
|
引用数 |
1
|
リソース情報 |
遺伝子材料 |
CSII-CMV-MCS-IRES2-Bsd (RDB04385)
pCMV-VSV-G-RSV-Rev (RDB04393)
pCAG-HIVgp (RDB04394). |