Anti-inflammatory effects of m-chlorophenylpiperazine in brain glia cells.
Glia cells are regarded as a mediator of neuroinflammation releasing pro-inflammatory cytokines and nitric oxide in the central nervous system. Microglia and astrocytes have been reported to play an important role in the progression of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. m-Chlorophenylpiperazine (m-CPP) is used clinically to manipulate serotonergic function, though its precise mechanisms of actions are not well understood. m-CPP alters synaptic transmission and neuronal function in vertebrates by non-selective agonistic actions on 5-HT1 and 5-HT2 receptors. In the present study, the anti-inflammatory effect of m-CPP was investigated in lipopolysaccharide (LPS)-stimulated microglia and astrocyte cultures. Our results showed that m-CPP significantly decreased the production of nitric oxide, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) in microglia and astrocyte cultures. m-CPP also attenuated the expression of inducible nitric oxide synthase and pro-inflammatory cytokines such as IL-1beta and TNF-alpha at mRNA levels. In addition, m-CPP inhibited nuclear factor-kappa B activation and phosphorylation of p38 mitogen-activated protein kinase in the LPS-stimulated microglia cells, providing molecular mechanisms of the anti-inflammatory effects. Moreover, m-CPP was neuroprotective as the drug reduced microglia-mediated neuroblastoma cell death in a microglia-neuron co-culture. These findings suggest that m-CPP may have important implications in the treatment of neuroinflammatory diseases.
Hwang
Jaegyu
J
Department of Pharmacology, School of Medicine, Brain Science and Engineering Institute, CMRI, Kyungpook National University, Daegu, South Korea.
Zheng
Long Tai
LT
Ock
Jiyeon
J
Lee
Maan Gee
MG
Suk
Kyoungho
K
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D002478:Cells, Cultured; D019610:Cytoprotection; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009457:Neuroglia / Q000187:drug effects*; D009569:Nitric Oxide / Q000096:biosynthesis; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010879:Piperazines; D017366:Serotonin Receptor Agonists; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D048051:p38 Mitogen-Activated Protein Kinases; C015068:1-(3-chlorophenyl)piperazine