| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Smith, Sylvia B. Liou, Gregory I. Gonsalvez, Graydon B. Bollinger, Kathryn E. Ha, Yonju Zhao, Jing |
| Description |
Country affiliation: United States Author Affiliation: Zhao J ( James and Jean Culver Vision Discovery Institute, Georgia Regents University, Augusta, Georgia, United States.); Ha Y ( James and Jean Culver Vision Discovery Institute, Georgia Regents University, Augusta, Georgia, United States Department of Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States.); Liou GI ( James and Jean Culver Vision Discovery Institute, Georgia Regents University, Augusta, Georgia, United States Department of Ophthalmology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States.); Gonsalvez GB ( Department of Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States.); Smith SB ( James and Jean Culver Vision Discovery Institute, Georgia Regents University, Augusta, Georgia, United States.); Bollinger KE ( James and Jean Culver Vision Discovery Institute, Georgia Regents University, Augusta, Georgia, United States.) |
| Abstract |
PURPOSE: To evaluate the effects of the σ 1 receptor (σR1) agonist, (+)-pentazocine, on lipopolysaccharide (LPS)-induced inflammatory changes in retinal microglia cells. METHODS: Retinal microglia cells were isolated from Sprague-Dawley rat pups. Cells were treated with LPS with or without (+)-pentazocine and with or without the σR1 antagonist BD1063. Morphologic changes were assayed. Cell viability was assessed by using MTT assay. Supernatant levels of tumor necrosis factor (TNF- ), interleukin 10, (IL-10), monocyte chemoattractant protein-1 (MCP-1), and nitric oxide (NO) were determined. Reactive oxygen species (ROS) formation was assayed, and levels of mitogen-activated protein kinases (MAPKs) were analyzed by using Western blot. RESULTS: The σR1 protein was expressed in retinal microglia. Incubation with LPS and/or (+)-pentazocine did not alter cell viability or σR1 protein levels. Incubation with LPS for 24 hours induced a marked change in microglial morphology and a significant increase in secreted levels of TNF- , IL-10, MCP-1, and NO. Pretreatment with (+)-pentazocine inhibited the LPS-induced morphologic changes. Release of TNF- , IL-10, MCP-1, and NO was reduced with (+)-pentazocine. Intracellular ROS formation was suppressed with (+)-pentazocine. Phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) was reduced in the presence of (+)-pentazocine. The σR1 antagonist BD1063 blocked the (+)-pentazocine-mediated inhibition of LPS-induced morphologic changes. In addition, BD1063 treatment blocked (+)-pentazocine-mediated suppression of LPS-induced TNF- , IL-10, MCP-1, NO, and intracellular ROS release. CONCLUSIONS: Treatment with (+)-pentazocine suppressed inflammatory responses of retinal microglia and inhibited LPS-induced activation of ERK/JNK MAPK. In neurodegenerative disease, (+)-pentazocine may exert neuroprotective effects through manipulation of microglia. |
| ISSN |
01460404 |
| e-ISSN |
15525783 |
| DOI |
10.1167/iovs.13-12823 |
| Journal |
Investigative Opthalmology & Visual Science |
| Issue Number |
6 |
| Volume Number |
55 |
| Language |
English |
| Publisher |
Association for Research in Vision and Ophthalmology |
| Publisher Date |
2014-05-08 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Microglia Drug Effects Pentazocine Pharmacology Receptors, Sigma Biosynthesis Retinal Ganglion Cells Pathology Retinitis Drug Therapy Animals Blotting, Western Cell Count Cell Survival Cytokines Metabolism Disease Models, Animal Enzyme-linked Immunosorbent Assay Immunohistochemistry Mitogen-activated Protein Kinases Optic Nerve Piperazines Rats, Sprague-dawley Reactive Oxygen Species Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Ophthalmology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Ophthalmology Sensory Systems Cellular and Molecular Neuroscience |
