Back to Search
Start Over
Naloxone inhibition of lipopolysaccharide-induced activation of retinal microglia is partly mediated via the p38 mitogen activated protein kinase signalling pathway.
- Source :
-
The Journal of international medical research [J Int Med Res] 2012; Vol. 40 (4), pp. 1438-48. - Publication Year :
- 2012
-
Abstract
- Objectives: To investigate the effects and underlying mechanism of action of naloxone on lipopolysaccharide (LPS)-induced activation of retinal microglia in vitro.<br />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.<br />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.<br />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 neuro degenerative diseases characterized by the activation of microglia.
- Subjects :
- Animals
Cells, Cultured
Enzyme Inhibitors pharmacology
Imidazoles pharmacology
Interleukin-1beta metabolism
Male
Microglia immunology
Microglia metabolism
Neurodegenerative Diseases metabolism
Neurodegenerative Diseases pathology
Phosphorylation
Primary Cell Culture
Protein Processing, Post-Translational drug effects
Pyridines pharmacology
Rats
Rats, Sprague-Dawley
Tumor Necrosis Factor-alpha metabolism
p38 Mitogen-Activated Protein Kinases metabolism
Lipopolysaccharides pharmacology
MAP Kinase Signaling System drug effects
Microglia drug effects
Naloxone pharmacology
Narcotic Antagonists pharmacology
Retina pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1473-2300
- Volume :
- 40
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of international medical research
- Publication Type :
- Academic Journal
- Accession number :
- 22971495
- Full Text :
- https://doi.org/10.1177/147323001204000422