Inhibitory effect of the antidepressant imipramine on NF-κB-dependent CXCL1 expression in TNFα-exposed astrocytes.
Neuroinflammation is associated with the pathophysiology of various neurodegenerative diseases. Emerging evidence indicates that imipramine, a tricyclic antidepressant commonly used in depressive disorders, exhibits neuroprotective activity partly through anti-inflammatory effects. However, the molecular mechanisms underlying imipramine-mediated anti-inflammatory response are poorly understood. In this study, rat primary cultured astrocytes were used to elucidate the effect of the imipramine on TNFα-induced inflammatory responses. The results clearly demonstrated that imipramine reduced TNFα-induced CXCL1 expression through suppression of NF-κB-dependent CXCL1 promoter activity in primary astrocytes. In addition, we found that imipramine suppressed TNFα-induced phosphorylation of inhibitor of κBα (IκBα) and p65/RelA nuclear factor-κB (NF-κB), as well as the nuclear translocation of p65/RelA in primary cultured astrocytes. Chemotaxis assay demonstrated that astrocyte-derived CXCL1 contributed to migration of BV2 microglial cells toward astrocytes. This response was significantly blocked by treatment of astrocytes with imipramine or NF-κB inhibitor BAY11-7082. This study indicates that the antidepressant imipramine inhibits TNFα-induced CXCL1 expression via down-regulation of NF-κB signaling pathway in astrocytes and suggests that imipramine has a potential as an anti-inflammatory drug.
Department of Biomedical Science and Technology, Research Center for Transcription Control, SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul 143-701, Republic of Korea.
Young Han
YH
Lee
Se Hyun
SH
Kim
Yeni
Y
Kim
Yoongho
Y
Lim
Kyooseob
K
Ha
Soon Young
SY
Shin
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000235:genetics / Q000276:immunology*; D007099:Imipramine / Q000494:pharmacology*; D016328:NF-kappa B / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000929:Antidepressive Agents, Tricyclic; D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007099:Imipramine