PMID- 24812552
OWN - NLM
STAT- MEDLINE
DCOM- 20140729
LR  - 20231213
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 55
IP  - 6
DP  - 2014 May 8
TI  - Sigma receptor ligand, (+)-pentazocine, suppresses inflammatory responses of 
      retinal microglia.
PG  - 3375-84
LID - 10.1167/iovs.13-12823 [doi]
AB  - PURPOSE: To evaluate the effects of the sigma 1 receptor (sigmaR1) 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 sigmaR1 antagonist BD1063. Morphologic 
      changes were assayed. Cell viability was assessed by using MTT assay. Supernatant 
      levels of tumor necrosis factor alpha (TNF-alpha), 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 sigmaR1 protein was expressed in retinal microglia. Incubation with LPS 
      and/or (+)-pentazocine did not alter cell viability or sigmaR1 protein levels. 
      Incubation with LPS for 24 hours induced a marked change in microglial morphology 
      and a significant increase in secreted levels of TNF-alpha, IL-10, MCP-1, and NO. 
      Pretreatment with (+)-pentazocine inhibited the LPS-induced morphologic changes. 
      Release of TNF-alpha, 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 sigmaR1 antagonist BD1063 blocked 
      the (+)-pentazocine-mediated inhibition of LPS-induced morphologic changes. In 
      addition, BD1063 treatment blocked (+)-pentazocine-mediated suppression of 
      LPS-induced TNF-alpha, 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.
CI  - Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
FAU - Zhao, Jing
AU  - Zhao J
AD  - James and Jean Culver Vision Discovery Institute, Georgia Regents University, 
      Augusta, Georgia, United States.
FAU - Ha, Yonju
AU  - Ha Y
AD  - 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.
FAU - Liou, Gregory I
AU  - Liou GI
AD  - 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.
FAU - Gonsalvez, Graydon B
AU  - Gonsalvez GB
AD  - Department of Cellular Biology and Anatomy, Medical College of Georgia, Georgia 
      Regents University, Augusta, Georgia, United States.
FAU - Smith, Sylvia B
AU  - Smith SB
AD  - James and Jean Culver Vision Discovery Institute, Georgia Regents University, 
      Augusta, Georgia, United States.
FAU - Bollinger, Kathryn E
AU  - Bollinger KE
AD  - James and Jean Culver Vision Discovery Institute, Georgia Regents University, 
      Augusta, Georgia, United States.
LA  - eng
GR  - K08 EY021758/EY/NEI NIH HHS/United States
GR  - R01 EY014560/EY/NEI NIH HHS/United States
GR  - 5K08EY021758-03/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140508
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (1-(2-(3,4-dichlorophenyl)ethyl)-4-methylpiperazine)
RN  - 0 (Cytokines)
RN  - 0 (Piperazines)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, sigma)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - RP4A60D26L (Pentazocine)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Count
MH  - Cell Survival/drug effects
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Immunohistochemistry
MH  - Microglia/*drug effects/metabolism/pathology
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Optic Nerve/metabolism/pathology
MH  - Pentazocine/*pharmacology
MH  - Piperazines/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, sigma/*biosynthesis/drug effects
MH  - Retinal Ganglion Cells/metabolism/*pathology
MH  - Retinitis/*drug therapy/metabolism/pathology
MH  - Sigma-1 Receptor
PMC - PMC4042630
OTO - NOTNLM
OT  - microglia
OT  - neuron-glia interactions
OT  - optic nerve
OT  - sigma receptor
EDAT- 2014/05/09 06:00
MHDA- 2014/07/30 06:00
PMCR- 2014/12/01
CRDT- 2014/05/10 06:00
PHST- 2014/05/10 06:00 [entrez]
PHST- 2014/05/09 06:00 [pubmed]
PHST- 2014/07/30 06:00 [medline]
PHST- 2014/12/01 00:00 [pmc-release]
AID - iovs.13-12823 [pii]
AID - 10.1167/iovs.13-12823 [doi]
PST - epublish
SO  - Invest Ophthalmol Vis Sci. 2014 May 8;55(6):3375-84. doi: 10.1167/iovs.13-12823.