کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2540600 1122600 2015 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Paroxetine differentially modulates LPS-induced TNFα and IL-6 production in mouse macrophages
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
Paroxetine differentially modulates LPS-induced TNFα and IL-6 production in mouse macrophages
چکیده انگلیسی


• Paroxetine, an FDA approved drug, distinctly regulates IL-6 and TNFα in macrophages.
• Fluoxetine, a drug belonging to the same class as paroxetine, mimics paroxetine.
• Mechanisms by which paroxetine regulates LPS-induced IL-6 and TNFα appear to be distinct.

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 phosphorylation, MAPK pathways were mostly unaffected. Together these data demonstrate that paroxetine has critical but differential effects on IL-6 and TNFα production in macrophages and that it likely regulates these cytokines via distinct mechanisms.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Immunopharmacology - Volume 25, Issue 2, April 2015, Pages 485–492
نویسندگان
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