In vitro inhibition of murine IFNγ production by phosphorothioate deoxyguanosine oligomers

Melissa D. Halpern, David S. Pisetsky

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Phosphorothioate (PT) oligonucleotides are designed as specific agents for antisense therapy although they have been reported to exert non-specific immunomodulatory effects. To elucidate further their actions, the effect of PT deoxyguanosine oligomers (S-oligo(dG)) on in vitro cytokine production by mouse splenocytes was studied. S-oligo(dG)20 inhibited production of INFγ induced by Con A, E. coli DNA or the combination of PMA and calcium ionophore A23187. The diester analogue was inactive, and of PT homo-oligomers tested, S-oligo(dG)20 was the most active. PT compounds with as few as 5 dG residues could also block INFγ production. These results indicate that base composition and length, as well as the PT backbone, contribute to the inhibition of INFγ production and extend the range of immunomodulatory effects of PT compounds.

Original languageEnglish (US)
Pages (from-to)47-52
Number of pages6
JournalImmunopharmacology
Volume29
Issue number1
DOIs
StatePublished - Feb 1995
Externally publishedYes

Keywords

  • Antisense therapy
  • Con A
  • Cytokine
  • IFNγ
  • IL-10
  • IL-12
  • IL-2
  • Interferon gamma
  • NK
  • PBS-BT
  • PBS-T
  • PMA
  • PT
  • Phosphorothioate oligonucleotide
  • S-oligo(dG)
  • TNFα
  • concanavalin A
  • dG
  • deoxyguanosine
  • interleukin 10
  • interleukin 12
  • interleukin 2
  • natural killer
  • phorbol myristate actetate
  • phosphate-buffered saline with 0.05% Tween 20
  • phosphate-buffered saline with 0.5% bovine serum albumin 0.4% Tween 20
  • phosphorothiate oligonucleotide
  • phosphorothioate deoxyguanosine oligomers
  • tumor necrosis factor alpha

ASJC Scopus subject areas

  • Pharmacology

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