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

International Journal of Molecular Sciences

Cheng-Chung Chen¹  Chih-Hsing Hung²  Chang-Hung Kuo³  Peng-Wei Wang⁴  Pinchen Yang⁴  Jui-Hsiu Tsai⁵  Kuang-Hung Cheng⁶ 

[1] Department of Community Psychiatry, Kai-Suan Psychiatric Hospital, 130 Kai-Suan 2nd Road, Kaohsiung 80276, Taiwan;Department of Pediatrics, Kaohsiung Municipal Hsiao-Kang Hospital,Kaohsiung Medical University, Kaohsiung 81267, Taiwan;Department of Pediatrics, Kaohsiung Municipal Ta-Tung Hospital,Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80761,Taiwan;Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80761, Taiwan;Department of Psychiatry, Kaohsiung Municipal Ta-Tung Hospital,Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80761, Taiwan;Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan;

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

DOI  :  10.3390/ijms150813223

来源: DOAJ

【 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) beforeLPS-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 inhibitedLPS-induced IP-10 expression via the mitogen-activated protein kinase (MAPK)-p38 pathway. Fluoxetine and bupropion could not only treat depression but also reduceTh1-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】

Unknown