IL-1-induced iNOS expression in human astrocytes via NF-κB

NITRIC oxide (NO) plays an important role in host defense as well as cell injury within the CNS. In contrast to rodent species, human astrocytes are the major glial source of NO. Although interleukin (IL)-1 stimulates astrocyte inducible NO synthase (iNOS) expression, the mechanism is poorly defined. In the present study using primary human fetal astrocyte cultures, we found that IL-1β stimulated activation of nuclear factor kappa B (NF- κB) within 2 h, iNOS mRNA expression at 8 h, and maximal NO production by 5 days post-treatment. This IL-l-induced activation of astrocyte iNOS was suppressed by pyrrolidine dithiocarbamate, an inhibitor of NF-κB activation, suggesting involvement of a NF-κB mechanism.