Inhibitory oligonucleotides block the induction of AP-1 transcription factor by stimulatory CpG oligonucleotides in B cells

Petar Lenert, Ae-Kyung Yi, Arthur M. Krieg, Laura L. Stunz, Robert F. Ashman

Research output: Contribution to journalArticle

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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-β-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.

Original languageEnglish (US)
Pages (from-to)143-150
Number of pages8
JournalAntisense and Nucleic Acid Drug Development
Volume13
Issue number3
DOIs
StatePublished - Jan 1 2003

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Oligonucleotides
B-Lymphocytes
Transcription Factors
Chemical activation
Cells
Galactosidases
Guanosine
Lipopolysaccharides
Cell Cycle
Apoptosis
Cell Line
pyrimidine

All Science Journal Classification (ASJC) codes

  • Genetics
  • Pharmacology

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Inhibitory oligonucleotides block the induction of AP-1 transcription factor by stimulatory CpG oligonucleotides in B cells. / Lenert, Petar; Yi, Ae-Kyung; Krieg, Arthur M.; Stunz, Laura L.; Ashman, Robert F.

In: Antisense and Nucleic Acid Drug Development, Vol. 13, No. 3, 01.01.2003, p. 143-150.

Research output: Contribution to journalArticle

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