Ar. Khaled et al., USE OF PHOSPHOROTHIOATE-MODIFIED OLIGODEOXYNUCLEOTIDES TO INHIBIT NF-KAPPA-B EXPRESSION AND LYMPHOCYTE FUNCTION, Clinical immunology and immunopathology, 86(2), 1998, pp. 170-179
NF-kappa B is a potential target for immunosuppressive therapy. Tao me
thods were evaluated to inhibit NF-kappa B: the antisense (AS) approac
h in which single-stranded oligodeoxynucleotides (ODNs) bind the mRNA
for the RelA subunit of NF-kappa B and the transcription factor decoy
(TFD) approach in which double-stranded ODNs hind the NF-kappa B prote
in. AS and TFD inhibited NF-kappa B binding and decreased total IgG an
d. anti-dsDNA antibody production in splenocytes from the BXSB/Yaa aut
oimmune mouse strain. TNF-alpha expression was reduced by AS and TFD,
as were the levels of IL-2, But AS effects did not last beyond 24 h, w
hereas TFD inhibited cytokine production after 72 h. AS had no effect
upon IL-6, while the TFD reduced the secretion of IL-6. Therefore, the
suppression of immune response mediators by AS of TFD, through inhibi
tion of NF-kappa B, is substantial, These inhibitors can serve as nove
l choices for therapy in the treatment of autoimmune disorders, (C) 19
98 Academic Press.