Journal article
Inhibitory Oligonucleotides Block the Induction of AP-1 Transcription Factor by Stimulatory CpG Oligonucleotides in B Cells
Antisense & nucleic acid drug development, Vol.13(3), pp.143-150
06/2003
DOI: 10.1089/108729003768247600
PMID: 12954114
Abstract
The proliferative response of primary B cells to CpG oligonucleotides (ODN) involves induction of nuclear activation promoting-1 (AP-1) transcription factor. AP-1 subunits c-Fos, Fos-B, Jun-B, and Jun-D, but not Fra-1 or Fra-2, were all induced by CpG ODNs in B cells within 30 minutes of stimulation, followed by c-Jun at 1-2 hours. c-Jun reached maximum at 6 hours. By 40 hours, Jun-B and Jun-D became dominant. Synthetic ODNs containing a single guanosine triplet/tetrad appropriately distanced from the 5' pyrimidine-rich unit, which inhibit CpG-driven cell cycle entry and apoptosis protection, blocked AP-1 induction by stimulatory ODNs when they were added simultaneously. After 30 minutes of stimulation, adding inhibitor no longer affected AP-1 at 6 hours. No AP-1 subunits escaped ODN inhibition. In a cell line transfected with an AP-1-beta-galactosidase reporter construct, CpG ODN-induced AP-1 transcriptional activity was prevented by inhibitory ODN, but lipopolysaccharide (LPS)-induced AP-1 activity was not. These data suggest that inhibitory ODNs block the CpG ODN-driven signaling pathway at a site proximal to AP-1 induction.
Details
- Title: Subtitle
- Inhibitory Oligonucleotides Block the Induction of AP-1 Transcription Factor by Stimulatory CpG Oligonucleotides in B Cells
- Creators
- Petar Lenert - Department of Internal Medicine, University of Iowa, College of Medicine, Iowa City, IA 52242Ae-Kyung Yi - Department of Internal Medicine, University of Iowa, College of Medicine, Iowa City, IA 52242Arthur M Krieg - Coley Pharmaceutical Group, Wellesley, MA 02481. 3Iowa City Veterans Administration Medical Center, Iowa City, IA 52240Laura L Stunz - Department of Internal Medicine, University of Iowa, College of Medicine, Iowa City, IA 52242 & Iowa City Veterans Administration Medical Center, Iowa City, IA 52240Robert F Ashman - Department of Internal Medicine, University of Iowa, College of Medicine, Iowa City, IA 52242 & Iowa City Veterans Administration Medical Center, Iowa City, IA 52240
- Resource Type
- Journal article
- Publication Details
- Antisense & nucleic acid drug development, Vol.13(3), pp.143-150
- DOI
- 10.1089/108729003768247600
- PMID
- 12954114
- ISSN
- 1087-2906
- eISSN
- 2168-6599
- Language
- English
- Date published
- 06/2003
- Academic Unit
- Microbiology and Immunology; Immunology; Internal Medicine
- Record Identifier
- 9984094601802771
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