IL-1-INDUCED INOS EXPRESSION IN HUMAN ASTROCYTES VIA NF-KAPPA-B

NITRIC Oxide (NO) plays an important role in host defense as well as c ell injury within the CNS. In contrast to rodent species, human astroc ytes are the major glial source of NO. Although interleukin (IL)-1 sti mulates astrocyte inducible NO synthase (iNOS) expression, the mechani sm is poorly defined. In the present study using primary human fetal a strocyte cultures, we found that IL-1 beta stimulated activation of nu clear factor kappa B (NF-kappa B) within 2 h, iNOS mRNA expression at 8 h, and maximal NO production by 5 days post-treatment. This IL-l-ind uced activation of astrocyte iNOS was suppressed by pyrrolidine dithio carbamate, an inhibitor of NF-kappa B activation, suggesting involveme nt of a NF-kappa B mechanism.