Inhibitory effects of indomethacin on nitric oxide production of BV-2 microglia stimulated by ?-amyloid 1-42 in vitro / 解放军医学杂志

ABSTRACT

Objective Inflammation is considered as a driving force in the pathogenesis of Alzheimer's disease. We study the inhibitory effects of indomethacin on production of nitric oxide (NO) in ?-amyloid 1-42 stimulated microglia in vitro, in order to explore the role of ?-amyloid and microglia in the pathogenesis of Alzheimer's disease, and that admimistration of anti-inflammatory drugs might be an effective therapeutic modality. Methods We cultured murine microglia BV-2 cells to serve as the model of microglia for experimentation in vitro. Indomethacin in different concentrations (10 -9 , 10 -8 , 10 -7 , 10 -6 and 10 -5 mol/L) was added separately without or with ?-amyloid 1-42 20?mol/L, and culture was continued for 12h. The production of nitric oxide (NO) and the activity of inducible nitric oxide synthase (iNOS) in the supernatant of culture were determined. iNOS mRNA expression was assessed by RT-PCR. Results There was no effect in the production of NO and the activity of iNOS in BV-2 cells incubated with indomethacin alone. Indomethacin could inhibit NO production and lower iNOS activity and iNOS mRNA expression after microglia were stimulated by ?-amyloid 1-42, and the inhibitory effect was obvious at the concentration of 10 -7 -10 -5 mol/L. Conclusions As a conventional non-steroidal anti-inflammatory drug (NSAIDs), indomethacin can inhibit NO production, decrease iNOS activity and iNOS mRNA expression in BV-2 microglia after being stimulated by ?-amyloid 1-42 in vitro. The results suggest that the mechanism by which indomethacin might be beneficial in treatment of AD might be due to the inhibition of NO production from microglia, blocking the inflammatory cascade reaction to ameliorate injury to neuron. As an effective model in vitro, BV-2 microglia are valuable in the study of Alzheimer's disease.