CpG DNA rescue from anti-IgM-induced WEHI-231 B lymphoma apoptosis via modulation of IκBα and IκNβ and sustained activation of nuclear factor- κB/c-Rel

Ae-Kyung Yi, Arthur M. Krieg

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Unmethylated CpG dinucleotides in particular base contexts in oligonucleotides (CpG DNA) rescue WEHI-231 cells from anti-IgM-induced cell cycle arrest and apoptosis. Anti-IgM rapidly elevated the levels of NFκB p50/c-Rel heterodimers followed by a decline of p50/c-Rel heterodimers by 3 h and a concomitant increase of p50/p50 homodimers. In contrast, CpG DNA induced and maintained the levels of p50/c-Rel heterodimers in the presence or absence of anti-IgM, while control non-CpG DNA failed to induce NFκB activation. Anti-IgM induced IκBα degradation followed by increased IκBα protein levels. The levels of IκBβ were increased after anti-IgM treatment. In contrast, CpG DNA, but not non-CpG DNA, induced sustained IκBα and IκBβ degradation in the presence or absence of anti-IgM. Inhibition of IκB degradation blocked CpG DNA-induced NFκB activation and expression of c- myc. Prevention of NFκB activation by inhibiting IκB degradation also suppressed the ability of CpG DNA to rescue WEHI-231 cells from anti-IgM- induced apoptosis. These results indicate that CpG DNA-mediated sustained activation of NFκB depends on the degradation of IκBα and IκBβ and is required for the CpG DNA-mediated anti-apoptosis gene expression and the protection against anti-IgM-induced apoptosis of WEHI-231 cells.

Original languageEnglish (US)
Pages (from-to)1240-1245
Number of pages6
JournalJournal of Immunology
Volume160
Issue number3
StatePublished - Feb 1 1998
Externally publishedYes

Fingerprint

Lymphoma
Apoptosis
DNA
anti-IgM
Cell Cycle Checkpoints
Oligonucleotides
Gene Expression
Proteins

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

@article{093049c713384db4b82fc02d47f70813,
title = "CpG DNA rescue from anti-IgM-induced WEHI-231 B lymphoma apoptosis via modulation of IκBα and IκNβ and sustained activation of nuclear factor- κB/c-Rel",
abstract = "Unmethylated CpG dinucleotides in particular base contexts in oligonucleotides (CpG DNA) rescue WEHI-231 cells from anti-IgM-induced cell cycle arrest and apoptosis. Anti-IgM rapidly elevated the levels of NFκB p50/c-Rel heterodimers followed by a decline of p50/c-Rel heterodimers by 3 h and a concomitant increase of p50/p50 homodimers. In contrast, CpG DNA induced and maintained the levels of p50/c-Rel heterodimers in the presence or absence of anti-IgM, while control non-CpG DNA failed to induce NFκB activation. Anti-IgM induced IκBα degradation followed by increased IκBα protein levels. The levels of IκBβ were increased after anti-IgM treatment. In contrast, CpG DNA, but not non-CpG DNA, induced sustained IκBα and IκBβ degradation in the presence or absence of anti-IgM. Inhibition of IκB degradation blocked CpG DNA-induced NFκB activation and expression of c- myc. Prevention of NFκB activation by inhibiting IκB degradation also suppressed the ability of CpG DNA to rescue WEHI-231 cells from anti-IgM- induced apoptosis. These results indicate that CpG DNA-mediated sustained activation of NFκB depends on the degradation of IκBα and IκBβ and is required for the CpG DNA-mediated anti-apoptosis gene expression and the protection against anti-IgM-induced apoptosis of WEHI-231 cells.",
author = "Ae-Kyung Yi and Krieg, {Arthur M.}",
year = "1998",
month = "2",
day = "1",
language = "English (US)",
volume = "160",
pages = "1240--1245",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - CpG DNA rescue from anti-IgM-induced WEHI-231 B lymphoma apoptosis via modulation of IκBα and IκNβ and sustained activation of nuclear factor- κB/c-Rel

AU - Yi, Ae-Kyung

AU - Krieg, Arthur M.

PY - 1998/2/1

Y1 - 1998/2/1

N2 - Unmethylated CpG dinucleotides in particular base contexts in oligonucleotides (CpG DNA) rescue WEHI-231 cells from anti-IgM-induced cell cycle arrest and apoptosis. Anti-IgM rapidly elevated the levels of NFκB p50/c-Rel heterodimers followed by a decline of p50/c-Rel heterodimers by 3 h and a concomitant increase of p50/p50 homodimers. In contrast, CpG DNA induced and maintained the levels of p50/c-Rel heterodimers in the presence or absence of anti-IgM, while control non-CpG DNA failed to induce NFκB activation. Anti-IgM induced IκBα degradation followed by increased IκBα protein levels. The levels of IκBβ were increased after anti-IgM treatment. In contrast, CpG DNA, but not non-CpG DNA, induced sustained IκBα and IκBβ degradation in the presence or absence of anti-IgM. Inhibition of IκB degradation blocked CpG DNA-induced NFκB activation and expression of c- myc. Prevention of NFκB activation by inhibiting IκB degradation also suppressed the ability of CpG DNA to rescue WEHI-231 cells from anti-IgM- induced apoptosis. These results indicate that CpG DNA-mediated sustained activation of NFκB depends on the degradation of IκBα and IκBβ and is required for the CpG DNA-mediated anti-apoptosis gene expression and the protection against anti-IgM-induced apoptosis of WEHI-231 cells.

AB - Unmethylated CpG dinucleotides in particular base contexts in oligonucleotides (CpG DNA) rescue WEHI-231 cells from anti-IgM-induced cell cycle arrest and apoptosis. Anti-IgM rapidly elevated the levels of NFκB p50/c-Rel heterodimers followed by a decline of p50/c-Rel heterodimers by 3 h and a concomitant increase of p50/p50 homodimers. In contrast, CpG DNA induced and maintained the levels of p50/c-Rel heterodimers in the presence or absence of anti-IgM, while control non-CpG DNA failed to induce NFκB activation. Anti-IgM induced IκBα degradation followed by increased IκBα protein levels. The levels of IκBβ were increased after anti-IgM treatment. In contrast, CpG DNA, but not non-CpG DNA, induced sustained IκBα and IκBβ degradation in the presence or absence of anti-IgM. Inhibition of IκB degradation blocked CpG DNA-induced NFκB activation and expression of c- myc. Prevention of NFκB activation by inhibiting IκB degradation also suppressed the ability of CpG DNA to rescue WEHI-231 cells from anti-IgM- induced apoptosis. These results indicate that CpG DNA-mediated sustained activation of NFκB depends on the degradation of IκBα and IκBβ and is required for the CpG DNA-mediated anti-apoptosis gene expression and the protection against anti-IgM-induced apoptosis of WEHI-231 cells.

UR - http://www.scopus.com/inward/record.url?scp=0031915373&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031915373&partnerID=8YFLogxK

M3 - Article

VL - 160

SP - 1240

EP - 1245

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -