Journal article
CpG Stimulation of Primary Mouse B Cells Is Blocked by Inhibitory Oligodeoxyribonucleotides at a Site Proximal to NF-κB Activation
Antisense & nucleic acid drug development, Vol.11(4), pp.247-256
08/01/2001
DOI: 10.1089/108729001317022241
PMID: 11572601
Abstract
Bacterial DNA and CpG-oligodeoxyribonucleotides (ODN) are powerful B cell activators, inducing apoptosis protection, cell cycle entry, proliferation, costimulatory molecule expression, immunoglobulin (Ig)
and interleukin-6 (IL-6) secretion. However, proximal events in B cell activation by ODN are only partially characterized, including the translocation of NF-
κ
B to the nucleus. In this paper,
we provide evidence that CpG-ODNinduced cell cycle entry and apoptosis protection are blocked by SN50 or gliotoxin and thus require NF-
κ
B activation. NF-
κ
B activation occurred
within 30 minutes of stimulation of murine B cells with a phosphorothioate (S) CpG-ODN and persisted for up to 40 hours, with p50, p65, and c-Rel as the major components. Similar to other NF-
κ
B
inducers, CpG-ODN caused an early I
κ
B
α
and I
κ
B
β
degradation plus cleavage of the p50 precursor and subsequent NF-
κ
B nuclear translocation.
A group of closely related S-ODN, which specifically blocked CpG-induced B cell activation at submicromolar concentrations, also prevented NF-
κ
B DNA binding and transcriptional activation.
These inhibitory S-ODN differed from stimulatory S-ODN by having 2-3 G substitutions in the central motif. As inhibitory S-ODN did not directly interfere with the NF-
κ
B DNA binding but prevented
CpG-induced NF-
κ
B nuclear translocation of p50, p65, and c-Rel and blocked p105, I
κ
B
α
, and I
κ
B
β
degradation, we concluded that their putative
target must lie upstream of inhibitory kinase (IKK) activation.
Details
- Title: Subtitle
- CpG Stimulation of Primary Mouse B Cells Is Blocked by Inhibitory Oligodeoxyribonucleotides at a Site Proximal to NF-κB Activation
- Creators
- Petar LenertLaura StunzAe-Kyung YiArthur M KriegRobert F Ashman
- Resource Type
- Journal article
- Publication Details
- Antisense & nucleic acid drug development, Vol.11(4), pp.247-256
- Publisher
- Mary Ann Liebert, Inc
- DOI
- 10.1089/108729001317022241
- PMID
- 11572601
- ISSN
- 1087-2906
- eISSN
- 2168-6599
- Language
- English
- Date published
- 08/01/2001
- Academic Unit
- Microbiology and Immunology; Immunology; Internal Medicine
- Record Identifier
- 9984094675502771
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