Fluoxetine increases the nitric oxide production via nuclear factor kappa B-mediated pathway in BV2 murine microglial cells.
A 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 (Nfkappab), an important upstream modulator for Nos2 expression, to find that fluoxetine increased DNA binding activity of Nfkappab. By Western blot analysis, phosphorylation levels of p38 mitogen-activated protein kinase (p38 Mapk, Mapk14) and extracellular signal-related kinase (Erk)1/2 Mapk, upstream signaling mediators of Nfkappab were found to be increased by fluoxetine. In addition, the mRNA expressions of other proinflammatory cytokines, interleukin 6 (Il6) and tumor necrosis factor alpha (Tnfalpha) were examined. The expressions of both Il6 and Tnfalpha by fluoxetine treatment were similar to those of Nos2 and Nfkappab. Taken together, our results show that fluoxetine stimulates NO production via Nfkappab-mediated pathway in BV2 cells.
Ha
Eunyoung
E
Department of Biochemistry, Kohwang Medical Research Institute, College of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea. eyha@khu.ac.kr
Jung
Kyung Hee
KH
Choe
Bong-Keun
BK
Bae
Jae-Hoon
JH
Shin
Dong-Hoon
DH
Yim
Sung-Vin
SV
Baik
Hyung Hwan
HH
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002460:Cell Line; D005473:Fluoxetine / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000096:biosynthesis / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013268:Stimulation, Chemical; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000928:Antidepressive Agents; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D005473:Fluoxetine; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II