Paroxetine's effect on the proinflammatory cytokine stimulation and intracellular signaling pathways in J774.2 cells

Naunyn Schmiedebergs Arch Pharmacol. 2023 Nov;396(11):3327-3335. doi: 10.1007/s00210-023-02669-1. Epub 2023 Aug 17.

Abstract

Paroxetine is extensively utilized in the management of depressive and anxious conditions. Paroxetine works by increasing serotonin levels in nerve cells in the brain. However, limited information is available regarding the direct effects of paroxetine on macrophage cells. Macrophages are a type of leukocytes involved in the body's immune response, playing a crucial role in combating infections. The impact of paroxetine on macrophages has been explored in research, although a comprehensive understanding is still pending. This study aimed to research the potential of administering paroxetine to J774.2 macrophage cells to stimulate the release of GM-CSF, TNF-α, IL-12p40, and IL-6 cytokines. Additionally, we examined the mechanisms of action of paroxetine on the p38 signaling pathway, which is involved in cytokine production, and the PI3K pathway, which is an important mechanism in intracellular signaling. Our findings revealed that paroxetine induced an inflammatory response in macrophages by promoting cytokine synthesis in a non-lipopolysaccharide (LPS) environment. We observed that paroxetine triggered the inflammatory response through the PI3K signaling pathway while suppressing the p38 signaling pathway.

Keywords: Cytokine; J774.2 cell line; Paroxetine; SSRI.

MeSH terms

  • Cytokines* / metabolism
  • Lipopolysaccharides / pharmacology
  • Paroxetine* / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cytokines
  • Paroxetine
  • Phosphatidylinositol 3-Kinases
  • Tumor Necrosis Factor-alpha
  • Lipopolysaccharides