title: Acetylsalicylic acid enhances the anti-inflammatory effect of fluoxetine through inhibition of NF-κB, p38-MAPK and ERK1/2 activation in lipopolysaccharide-induced BV-2 microglia cells.
abstract: The latest advancements in neurobiological research provide increasing evidence that inflammatory and neurodegenerative pathways play an important role in depression. According to the cytokine hypothesis, depression could be due to the increased production of pro-inflammatory cytokines by microglia activation. Thus, using the BV-2 microglial cell line, the aim of the present study was to investigate whether fluoxetine (FLX) or acetylsalicylic acid (ASA) could inhibit this microglia activation and could achieve better results in combination. Our results showed that FLX could attenuate lipopolysaccharide (LPS)-induced production of interleukin-1β (IL-1β), the expression of the indoleamine 2,3 dioxygenase (IDO) enzyme and the depletion of 5-HT. Moreover, FLX could inhibit phosphorylation of nuclear factor-κB (NF-κB) and phosphorylation of p38 mitogen-activated protein kinase (MAPK), and the combined use with ASA could enhance these effects. Notably, the adjunctive agent ASA could also inhibit phosphorylation of extracellular-regulated kinase 1/2 (ERK1/2). Taken together, our results suggest that FLX may have some anti-inflammatory effects by modulating microglia activation and that ASA served as an effective adjunctive agent by enhancing these therapeutic effects.
authors: Anhui Provincial Cancer Hospital, Hefei, Anhui Province, China.
authors: J M
authors: JM
authors: Yang
authors: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine of China Education Ministry, Hefei, Anhui Province, China.
authors: B B
authors: BB
authors: Rui
authors: High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, Anhui Province, China.
authors: C
authors: C
authors: Chen
authors: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine of China Education Ministry, Hefei, Anhui Province, China.
authors: H
authors: H
authors: Chen
authors: Anhui Provincial Hospital, Hefei, Anhui Province, China.
authors: T J
authors: TJ
authors: Xu
authors: Anhui Provincial Hospital, Hefei, Anhui Province, China. Electronic address: xu_weiping666@163.com.
authors: W P
authors: WP
authors: Xu
authors: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine of China Education Ministry, Hefei, Anhui Province, China. Electronic address: wwei@ahmu.edu.cn.
authors: W
authors: W
authors: Wei
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005473:Fluoxetine / Q000494:pharmacology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D018687:Antidepressive Agents, Second-Generation; D008070:Lipopolysaccharides; D016328:NF-kappa B; D005473:Fluoxetine; D048051:p38 Mitogen-Activated Protein Kinases; D001241:Aspirin
keywords: acetylsalicylic acid; depression; fluoxetine; microglia