Paroxetine differentially modulates LPS-induced TNFα and IL-6 production in mouse macrophages

International Immunopharmacology
Haritha DurairajNarayanan Parameswaran

Abstract

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) that is clinically used for the treatment of depression in human patients. Because of recent reports on the role of serotonin in modulating inflammation and the link between inflammation and depression, we sought to test the effect of paroxetine directly on macrophage response to an inflammatory stimulus. Lipopolysaccharide (LPS) treatment of mouse macrophages significantly enhanced TNFα and IL-6 production. Paroxetine treatment of macrophages, however, significantly inhibited LPS-induced IL-6 production. In contrast, paroxetine enhanced LPS-induced TNFα production in macrophages. These effects of paroxetine were mimicked by fluoxetine, another SSRI. To determine if the effects of paroxetine are mediated via modulation of the 5-HT system, we treated macrophages with 5-HT or 5-HT receptor antagonist (LY215840) in the presence of LPS and/or paroxetine. 5-HT treatment by itself did not affect LPS-induced cytokine production. LY215840, however, reversed paroxetine's effect on LPS-induced TNFα production but not IL-6. To understand the signaling mechanisms, we examined paroxetine's effect on MAPK and NFκB pathways. While paroxetine inhibited LPS-induced IκBα phosphorylati...Continue Reading

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Citations

Mar 28, 2017·ACS Chemical Neuroscience·Matthew J RobsonRandy D Blakely
Apr 8, 2016·Experimental Biology and Medicine·Katarzyna NazimekIwona Filipczak-Bryniarska
Aug 1, 2018·Cellular and Molecular Neurobiology·V S Suvanish KumarG K Rajanikant
Feb 6, 2020·Journal of Biochemical and Molecular Toxicology·Mahdieh KabiriAlireza Karimollah
Jun 3, 2017·The Biochemical Journal·Michael D SteuryNarayanan Parameswaran
Feb 12, 2021·Science Translational Medicine·Elijah L CarlsonFadia Kamal
Mar 11, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Justin Fortune CreedenCheryl B McCullumsmith
Jan 7, 2018·Developmental and Comparative Immunology·Yunke JiaLinsheng Song
Jun 18, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Gerber AdamD'Armiento Jeanine
Jul 14, 2021·Neuropsychopharmacology Reports·Claire Kyung Sun MeikleRandall G Worth

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