Inhibitory effects of indomethacin on nitric oxide and interleukin-1β production in β-amyloid1-42 stimulated BV-2 microglia in vitro

Objective To study the inhibitory ef fects of indomethacin on production of nitric oxide(NO)and interleukin-1β(I L-1β)in β-amyloid1-42stimulated microglia in vitro in orde r to explore the role of β-amyloid and microglia in the pathogenesis of Alzhei mer's disease(AD)and whether anti-inflammatory drugs might be an effective fo rm of therapy.Methods Murine microglia BV-2 cells were cultured as the model of microglia in vitro.Different concentrations of indomethacin(10-9,10-8,10-7,10-6,10-5mol/L)were added without or with β-amyloid1-42 20μmol/L and cultured continuously for 12h.The produ ction of NO and IL-1β was studied and iNOS mRNA and IL-1β mRNA expression we re assessed by RT-PCR.Results There was no influence on the production of NO and IL-1 β,and expression of iNOS mRNA and IL-1β mRNA in BV-2 cells incubated with i ndomethacin alone.β Amyloid1-42 could stimulate BV-2 cells to produce NO and IL-1β and enhance expression of iNOS mRNA and IL-1 mRNA.Indomethacin could inhibit NO and IL-1β production and lower iNOS mRNA and IL-1β mRNA expressi on in BV-2 cells stimulated!by β-amyloid1-42,and the inhibitory effect was obvious at the concentrations of 10-7-10-5mol/L.Conclusion As a conventional non-steroidal anti-inflammatory dru g,indomethacin could inhibit NO and IL-1β production and decrease iNOS mRNA and IL-1β mRNA expression in BV-2 microglia stimulated by β-amyloid1-42 in vitro.The results suggest that the mechanism by which indom ethacin berng beneficial to treatment of AD might be due to the inhibition of NO production from microglia,blocking the inflammatory cascade reaction and reduc ing injury of neuron.As an effective model in vitro,BV-2 micr oglia are valuable in the study of AD.