Although N-acetyl-L-aspartate (NAA) has been shown to be important to myelin synthesis and osmotic regulation, the biological rationale for the high levels of NAA found in the brain remains unknown. Here, a human astroglial cell line (STTG) was treated with NAA and stimulated with ionomycin, ionomycin/PMA, or IL-1beta. PGE(2) levels in ionomycin-stimulated STTG cells decreased by 76% and > 95% at NAA concentrations of 10 and 20mM, respectively. NAA also decreased the levels of COX-2 protein and activated NF-kappaB in IL-1beta-stimulated STTG cells but had little effect on unstimulated cells. Also, NAA significantly decreased intracellular calcium levels in ionomycin/PMA-stimulated cells. NAA had no effect on total COX-2 activity or COX-2 mRNA. Acetylation of IkappaBalpha kinase, an acetylation target of aspirin, was not observed when NAA was present. These results demonstrate that NAA appears to be important in the modulation of inflammation in the human STTG astroglial cell line. The results of these findings are discussed in relation to neuronal pathologies that exhibit abnormal NAA levels within the brain.