Phenelzine potentiates production of proinflammatory cytokines via the NF-κB pathway in LPS-activated microglia cells (112.11)

Abstract

Abstract Phenelzine is a potent monoamine oxidase (MAO) inhibitor that is widely used and has been shown to be clinically efficacious in patients with depression. It is also well known that nitric oxide (NO) synthase inhibitors show preclinical antidepressant-like properties, which suggests that NO is involved in the pathogenesis of depression. The purpose of this study was to determine if phenelzine affects the production of NO and tumor necrosis factor-alpha (TNF- α) in activated BV-2 microglia cells. Phenelzine increased the lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase (iNOS), as well as the release of TNF- α and IL-6 in BV-2 microglia cells. It is also confirmed that phenelzine increased the levels of NO, TNF-α and IL-6 in LPS-activated primary microglia cells. Phenelzine increased nuclear translocation of NF-κB by phospholylation of IκB-α in LPS-activated microglia cells. Taken together, these findings suggest that high doses of phenelzine could aggravate inflammatory responses in microglia cells that are mediated by NO and TNF-α.