Stimulation of Alpha7 Nicotinic Acetylcholine Receptor Attenuates Nicotine-Induced Upregulation of MMP, MCP-1, and RANTES through Modulating ERK1/2/AP-1 Signaling Pathway in RAW264.7 and MOVAS Cells
| Autor: | Qiuyan Dai, Liping Liu, Qunan Cao, Zhen-Zhen Guo, Anmin Ren, Hongxian Wu |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Nicotine medicine.medical_specialty Article Subject alpha7 Nicotinic Acetylcholine Receptor MAP Kinase Signaling System T cell Immunology Inflammation 030204 cardiovascular system & hematology Pharmacology Proinflammatory cytokine Bridged Bicyclo Compounds Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Internal medicine Nitriles lcsh:Pathology Butadienes medicine Animals Phosphorylation Extracellular Signal-Regulated MAP Kinases Chemokine CCL5 Chemokine CCL2 Acetylcholine receptor Chemistry Monocyte JNK Mitogen-Activated Protein Kinases Cell Biology Matrix Metalloproteinases Up-Regulation Transcription Factor AP-1 RAW 264.7 Cells 030104 developmental biology medicine.anatomical_structure Endocrinology Benzamides medicine.symptom Signal transduction lcsh:RB1-214 Research Article Signal Transduction medicine.drug |
| Zdroj: | Mediators of Inflammation Mediators of Inflammation, Vol 2017 (2017) |
| ISSN: | 1466-1861 0962-9351 |
| DOI: | 10.1155/2017/2401027 |
| Popis: | Vagus nerve stimulation through alpha7 nicotine acetylcholine receptors (α7-nAChR) signaling had been demonstrated attenuation of inflammation. This study aimed to determine whether PNU-282987, a selective α7-nAChR agonist, affected activities of matrix metalloproteinase (MMP) and inflammatory cytokines in nicotine-treatment RAW264.7 and MOVAS cells and to assess the underlying molecular mechanisms. RAW264.7 and MOVAS cells were treated with nicotine at different concentrations (0, 1, 10, and 100 ng/ml) for 0–120 min. Nicotine markedly stimulated the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) and c-Jun in RAW264.7 cells. Pretreatment with U0126 significantly suppressed phosphorylation of ERK1/2 and further attenuated nicotine-induced activation of c-Jun and upregulation of MMP-2, MMP-9, monocyte chemotactic protein- (MCP-) 1, and regulated upon activation normal T cell expressed and secreted (RANTES). Similarly, nicotine treatment also increased phosphorylation of c-Jun and expressions of MMP-2, MMP-9, MCP-1, and RANTES in MOVAS cells. When cells were pretreated with PNU-282987, nicotine-induced activations of ERK1/2 and c-Jun in RAW264.7 cells and c-Jun in MOVAS cells were effectively inhibited. Furthermore, nicotine-induced secretions of MMP-2, MMP-9, MCP-1, and RANTES were remarkably downregulated. Treatment with α7-nAChR agonist inhibits nicotine-induced upregulation of MMP and inflammatory cytokines through modulating ERK1/2/AP-1 signaling in RAW264.7 cells and AP-1 in MOVAS cells, providing a new therapeutic for abdominal aortic aneurysm. |
| Databáze: | OpenAIRE |
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