Involvement of NF-κB activation in the induction of type II nitric oxide synthase in human glioblastoma cells

Nitric oxide (NO) produced by glial cells has been implicated in the pathogenesis of neurodegenerative diseases. In human glial cells, the transcriptional mechanism of inducible NO synthase (iNOS) remains to be understood. We examined the role of the transcription factor NF-xB in the induction of iNOS in a human glioblastoma cell line, A-172. Treatment of A-172 cells with lipopolysaccharide (LPS), interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma) induced iNOS mRNA and protein expression subsequent to the degradation of I Chi B, a protein that inhibits NF-Chi B, and the DNA binding of NF-Chi B. Furthermore, the antioxidant pyrroridine dithiocarbamate (PDTC), which is known to inhibit NF-Chi B activation, inhibited nitrite production in a dose-dependent manner. The inhibitory effect of PDTC correlated with the prevention of I Chi B degradation. Another antioxidant, nordihydroguaiaretic acid (NDGA), also inhibited the nitrite formation and iNOS mRNA expression through its preventive effect on NF-Chi B activation. These results suggest the involvement of NF-Chi B activation in iNOS induction in human glial cells.