Naloxone Inhibition of Lipopolysaccharide-Induced Activation of Retinal Microglia is Partly Mediated via the p38 Mitogen Activated Protein Kinase Signalling Pathway
| Autor: | Qin Yw, Fu Ll, Ni Yq, Jiawen Fan, Chun Jiang, Yingxiao Xu |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Lipopolysaccharides
Male MAPK/ERK pathway medicine.medical_specialty Lipopolysaccharide MAP Kinase Signaling System Pyridines Narcotic Antagonists p38 mitogen-activated protein kinases Interleukin-1beta Primary Cell Culture (+)-Naloxone Pharmacology p38 Mitogen-Activated Protein Kinases Biochemistry Retina Rats Sprague-Dawley chemistry.chemical_compound Internal medicine medicine Animals Enzyme Inhibitors Phosphorylation Cells Cultured Microglia Naloxone Tumor Necrosis Factor-alpha business.industry Biochemistry (medical) Imidazoles Interleukin Neurodegenerative Diseases Cell Biology General Medicine Rats medicine.anatomical_structure Endocrinology Mechanism of action chemistry Tumor necrosis factor alpha medicine.symptom business Protein Processing Post-Translational |
| Zdroj: | Journal of International Medical Research. 40:1438-1448 |
| ISSN: | 1473-2300 0300-0605 |
| Popis: | OBJECTIVES: To investigate the effects and underlying mechanism of action of naloxone on lipopolysaccharide (LPS)-induced activation of retinal microglia in vitro. METHODS: Rat retinal microglia primary cultures were divided into four treatment groups: untreated; 1 μg/ml LPS for 12 h; 0.5, 1.0 or 2.0 μM naloxone for 30 min before LPS; 2.5 or 5.0 μM SB203580 for 12 h before LPS and naloxone. Levels of tumour necrosis factor (TNF)-α and interleukin (IL)-1β were determined by enzyme-linked immuno sorbent assay. Western blot analysis and double immunofluorescence were used to examine activation of the mitogen activated protein kinase (MAPK) signalling pathway. RESULTS: LPS induced an increase in TNF-α and IL-1β in culture supernatants, which was dose-dependently inhibited by naloxone. Naloxone also dose-dependently inhibited LPS-induced increases in phosphorylated p38 MAPK. Pretreatment of cells with SB203580 attenuated the inhibitory effect of naloxone on TNF-α and IL-1β production. CONCLUSIONS: Naloxone suppressed LPS-induced activation of cultured retinal microglia and this suppression appeared to occur partly through the p38 MAPK signalling pathway. Naloxone may have therapeutic potential in neurodegenerative diseases characterized by the activation of microglia. |
| Databáze: | OpenAIRE |
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