Effects of Antidepressants on IP-10 Production in LPS-Activated THP-1 Human Monocytes

International Journal of Molecular Sciences

Jui-Hsiu Tsai¹  Chang-Hung Kuo³  Pinchen Yang⁴  Kuang-Hung Cheng⁵  Peng-Wei Wang⁴  Cheng-Chung Chen² 

[1] Department of Psychiatry, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80761, Taiwan; E-Mail:;Department of Community Psychiatry, Kai-Suan Psychiatric Hospital, 130 Kai-Suan 2nd Road, Kaohsiung 80276, Taiwan; E-Mail:;Department of Pediatrics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80761, Taiwan; E-Mail:;Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80761, Taiwan; E-Mails:;Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan; E-Mail:

关键词: antidepressants;    IP-10;    chemokine;    monocyte;    LPS;   

DOI  :  10.3390/ijms150813223

来源: mdpi

【 摘 要 】

Major 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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.