Effects of Antidepressants on IP-10 Production in LPS-Activated THP-1 Human Monocytes
AbstractMajor depressive disorder and cardiovascular disease are common serious illnesses worldwide. Selective serotonin reuptake inhibitors and norepinephrine-dopamine reuptake inhibitors may reduce the mortality of cardiovascular disease patients with comorbid depression. Interferon-γ-inducible protein 10 (IP-10), a type 1 T helper cell (Th1)-related chemokine, contributes to manifestations of atherosclerosis during cardiovascular inflammations; however, the pathophysiological mechanisms linking cardiovascular disease and effective antidepressants have remained elusive. We investigated the in vitro effects of six different classes of antidepressants on the IP-10 chemokine expression in lipopolysaccharide (LPS)-stimulated monocytes, and their detailed intracellular mechanisms. The human monocytes were pretreated with antidepressants (10−8–10−5 M) before LPS-stimulation. IP-10 was measured by enzyme-linked immunosorbent assay (ELISA) and then intracellular signaling was investigated using Western blotting and chromatin immunoprecipitation. Fluoxetine and bupropion suppressed LPS-induced IP-10 expression in monocytes, and they had no cytotoxic effects. Furthermore, fluoxetine inhibited LPS-induced IP-10 expression via the mitogen-activated protein kinase (MAPK)-p38 pathway. Fluoxetine and bupropion could not only treat depression but also reduce Th1-related chemokine IP-10 production in human monocytes. Our results may indicate a possible mechanism related to how particular antidepressants reduce the risk of cardiovascular disease. View Full-Text
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Tsai, J.-H.; Kuo, C.-H.; Yang, P.; Cheng, K.-H.; Wang, P.-W.; Chen, C.-C.; Hung, C.-H. Effects of Antidepressants on IP-10 Production in LPS-Activated THP-1 Human Monocytes. Int. J. Mol. Sci. 2014, 15, 13223-13235.
Tsai J-H, Kuo C-H, Yang P, Cheng K-H, Wang P-W, Chen C-C, Hung C-H. Effects of Antidepressants on IP-10 Production in LPS-Activated THP-1 Human Monocytes. International Journal of Molecular Sciences. 2014; 15(8):13223-13235.Chicago/Turabian Style
Tsai, Jui-Hsiu; Kuo, Chang-Hung; Yang, Pinchen; Cheng, Kuang-Hung; Wang, Peng-Wei; Chen, Cheng-Chung; Hung, Chih-Hsing. 2014. "Effects of Antidepressants on IP-10 Production in LPS-Activated THP-1 Human Monocytes." Int. J. Mol. Sci. 15, no. 8: 13223-13235.