Mz. Ding et al., ANTISENSE BLOCKADE OF INDUCIBLE NITRIC-OXIDE SYNTHASE IN GLIAL-CELLS DERIVED FROM ADULT SJL MICE, Neuroscience letters, 220(2), 1996, pp. 89-92
Increasing evidence suggests a correlation between cytokine-induced ni
tric oxide synthase (iNOS) and demyelination in Multiple sclerosis (MS
). Inhibition of iNOS may therefore be a novel therapeutic approach in
MS. To test an antisense oligodeoxynucleotide (ODN) knockdown strateg
y for inhibiting iNOS, we used lipopolysaccharide (LPS) together with
gamma-interferon (IFN-gamma) to induce iNOS in adult mouse mixed glial
cell cultures. We administered an iNOS-derived antisense phosphorothi
orate oligodeoxynucleotide (S-ODN) to block the induction. The antisen
se ODN treatment resulted in significant inhibition of LPS and IFN-gam
ma induced iNOS mRNA and protein expression. It also inhibited nitric
oxide (NO) and cyclic GMP (cGMP) production in a dose dependent fashio
n. Sense and random S-oligo had no effect in any of these studies. The
se data indicate the efficacy and specificity of the antisense oligode
oxynucleotide approach in inhibiting iNOS in glial cells. Copyright (C
) 1996 Elsevier Science Ireland Ltd.