title: Effects of antidepressants on IP-10 production in LPS-activated THP-1 human monocytes.
abstract: 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.
authors: Department of Psychiatry, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80761, Taiwan. d880340@kmu.edu.tw.
authors: Jui-Hsiu
authors: JH
authors: Tsai
authors: Department of Pediatrics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80761, Taiwan. kuochanghung.dr@gmail.com.
authors: Chang-Hung
authors: CH
authors: Kuo
authors: Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80761, Taiwan. pinchen@kmu.edu.tw.
authors: Pinchen
authors: P
authors: Yang
authors: Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan. khcheng@faculty.nsysu.edu.tw.
authors: Kuang-Hung
authors: KH
authors: Cheng
authors: Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80761, Taiwan. 990107@mail.hmuh.org.tw.
authors: Peng-Wei
authors: PW
authors: Wang
authors: Department of Community Psychiatry, Kai-Suan Psychiatric Hospital, 130 Kai-Suan 2nd Road, Kaohsiung 80276, Taiwan. ccchen@kcg.gov.tw.
authors: Cheng-Chung
authors: CC
authors: Chen
authors: Department of Pediatrics, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung 81267, Taiwan. pedhung@gmail.com.
authors: Chih-Hsing
authors: CH
authors: Hung
mesh_terms: D000928:Antidepressive Agents / Q000494:pharmacology*; D016642:Bupropion / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D054357:Chemokine CXCL10 / Q000032:analysis*; D047369:Chromatin Immunoprecipitation; D004797:Enzyme-Linked Immunosorbent Assay; D005473:Fluoxetine / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D054357:Chemokine CXCL10; D008070:Lipopolysaccharides; D005473:Fluoxetine; D016642:Bupropion; D048051:p38 Mitogen-Activated Protein Kinases