Fluoxetine increases the nitric oxide production via nuclear factor kappa B-mediated pathway in BV2 murine microglial cells

body of recent evidence implicates that antidepressants affect the inflammatory response and immune system. The present study is focused on the effects of the most widely used antidepressant agent, fluoxetine on the production of nitric oxide (NO) in BV2 microglial cells. In this study, we observed interesting result that NO production was increased by fluoxetine. The mRNA level of nitric oxide synthase (iNos, Nos2) by RT-PCR was also stimulated by fluoxetine. We next conducted electophoretic mobility shift assay (EMSA) to determine the DNA binding activity of nuclear factor kappa B (Nf kappa b), an important upstream modulator for Nos2 expression, to find that fluoxetine increased DNA binding activity of Nf kappa b. By Western blot analysis, phosphorylation levels of p38 mitogen-activated protein kinase (p38 Mapk, Mapk`14) and extracellular signal-related kinase (Erk)1/2 Mapk, upstream signaling mediators of Nf kappa b were found to be increased by fluoxetine. In addition, the mRNA expressions of other proinflammatory cytokines, interleukin 6 (116) and tumor necrosis factor alpha (Thf alpha) were examined. The expressions of both 116 and Tnf alpha by fluoxetine treatment were similar to those of Nos2 and Nf kappa b. Taken together, our results show that fluoxetine stimulates NO production via Nf kappa b-mediated pathway in BV2 cells. (c) 2005 Elsevier Ireland Ltd. All rights reserved.