Paroxetine suppresses 27-hydroxycholesterol-induced responses in THP-1 human monocytic cells by regulating the...

Paroxetine (PRX) is widely prescribed for treating psychiatric disorders. Emerging evidence suggests that PRX can act as an immunosuppressive agent, yet the molecular mechanisms underlying its effects are not fully understood. This study has investigated whether PRX influences phenotypic changes of monocytic cells and signaling pathways induced by immune oxysterol, like 27-hydroxycholesterol (27OHChol), that triggers an inflammatory response using THP-1 monocytic cells. Treatment with PRX impaired 27OHChol-induced transcription and production of the pro-inflammatory chemokine CCL2, which was associated with decreased migration of monocytic cells, and repressed the expression and activity of MMP-9. It reduced the expression of mature dendritic cell markers, like CD80, CD83, and CD88, and partially restored phagocytic function. PRX also impaired phosphorylation of Akt and the downstream targets of mTORC1, S6, and 4E-BP1. These results indicate that PRX suppresses 27OHChol-induced change of monocytic cells to a proinflammatory phenotype by influencing the Akt/mTORC1 pathway. We suggest that PRX exerts its anti-inflammatory effects by suppressing the activation of monocytic cells in response to immune oxysterol.