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Tlr4 and mu opioid receptor

Nan Xie, Nicholas Matigian, Tharindu Vithanage, Kye Gregory, Zeyad D Nassar, Peter J Cabot, Paul N Shaw, Carl M J Kirkpatrick, Kim-Anh Lê Cao, David Sturgess, Marie-Odile Parat
Purpose: The purpose of this study is to investigate the potential interplay between opioid analgesia and tumor metastasis through modulation of μ-opioid receptor (MOR), Toll-like receptor 4 (TLR4) activation, and matrix degradation potential. Experimental Design: Plasma samples were collected from 60 patients undergoing elective lower limb joint replacement preoperatively and at 3, 6, and 24 hours after surgery; pain scores were documented at the same time points. Opioid administration was recorded and converted into morphine IV equivalents...
May 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yiming Meng, Xinghua Gao, Wenna Chen, Nicolas P Plotnikoff, Noreen Griffin, Guirong Zhang, Fengping Shan
MENK, an endogenous opioid peptide has been reported to have many immunological and antitumor activities. So far the detailed mechanisms of antitumor through regulating DCs by MENK have not been elucidated yet. The aim of this work was to investigate the antitumor mechanisms of MENK via regulating DC. The monitoring methods, such as ELISA, MTS assay, CFSE, Real-time PCR and Western blot were included in our research. We found bone marrow derived dendritic cells (BMDCs) in 36 female C57BL/6 mice treated with MENK enhanced expression of key surface molecules, increased production of critical cytokines reduced endocytosis of FITC-dextran, upregulated TLR4 through MyD88/NF-κB signaling pathway and mounted higher antitumor activity...
March 2017: International Immunopharmacology
P M Grace, K M Ramos, K M Rodgers, X Wang, M R Hutchinson, M T Lewis, K N Morgan, J L Kroll, F R Taylor, K A Strand, Y Zhang, D Berkelhammer, M G Huey, L I Greene, T A Cochran, H Yin, D S Barth, K W Johnson, K C Rice, S F Maier, L R Watkins
CNS immune signaling contributes to deleterious opioid effects including hyperalgesia, tolerance, reward, and dependence/withdrawal. Such effects are mediated by opioid signaling at toll-like receptor 4 (TLR4), presumptively of glial origin. Whether CNS endothelial cells express TLR4 is controversial. If so, they would be well positioned for activation by blood-borne opioids, contributing to opioid-induced pro-inflammatory responses. These studies examined adult primary rat CNS endothelial cell responses to (-)-morphine or its mu opioid receptor (MOR)-inactive metabolite morphine-3-glucuronide (M3G), both known TLR4 agonists...
November 7, 2014: Neuroscience
Mohsen Zhaleh, Marzieh Panahi, Mehri Ghafurian Broujerdnia, Rostam Ghorbani, Kambiz Ahmadi Angali, Ghasem Saki
BACKGROUND: Opioid drugs are used in the treatment of acute post-surgical pain and chronic pain, such as those associated with cancer. Opioid used is associated with complications such as analgesic tolerance, dependence and opioid abuse. The molecular mechanisms of unwanted opioid responses are varied but recent advances have highlighted elevations in pro-inflammatory cytokines and pro-inflammatory glial following chronic administration of morphine. In this study we investigated the neurodegenerative effects of morphine through its effects on Toll-Like Receptor 4 (TLR4) in the male rat hippocampus and evaluated the level of Interleukin-1 beta (IL-1β)...
July 2014: Journal of Injury & Violence Research
C W Stevens, S Aravind, S Das, R L Davis
BACKGROUND AND PURPOSE: Previous work in our laboratory showed opioid agents inhibit cytokine expression in astrocytes. Recently, Watkins and colleagues hypothesized that opioid agonists activate toll-like receptor 4 (TLR4) signalling, which leads to neuroinflammation. To test this hypothesis, we characterized LPS and opioid effects on TLR4 signalling in reporter cells. EXPERIMENTAL APPROACH: NF-κB reporter cells expressing high levels of TLR4 were used to compare LPS and opioid effects on NF-κB activation, a pathway activated by TLR4 stimulation...
March 2013: British Journal of Pharmacology
Silvia Franchi, Sarah Moretti, Mara Castelli, Donatella Lattuada, Cinzia Scavullo, Alberto E Panerai, Paola Sacerdote
Opioids have been shown to affect both innate and adaptive immunity. We previously showed that morphine affects the macrophage production of pro-inflammatory cytokines after LPS in a NFkB dependent manner. Toll like receptors (TLRs) play a crucial role in the signaling pathways which lead to NFkB activation. TLR4 is considered the Lipopolysaccaride (LPS) receptor. The data here presented show that, in murine macrophages, morphine impacts on the immune function acting on the early step of pathogen recognition...
March 2012: Brain, Behavior, and Immunity
S S Lewis, M R Hutchinson, N Rezvani, L C Loram, Y Zhang, S F Maier, K C Rice, L R Watkins
Morphine-3-glucoronide (M3G) is a major morphine metabolite detected in cerebrospinal fluid of humans receiving systemic morphine. M3G has little-to-no affinity for opioid receptors and induces pain by unknown mechanisms. The pain-enhancing effects of M3G have been proposed to significantly and progressively oppose morphine analgesia as metabolism ensues. We have recently documented that morphine activates toll-like receptor 4 (TLR4), beyond its classical actions on mu-opioid receptors. This suggests that M3G may similarly activate TLR4...
January 20, 2010: Neuroscience
Mark R Hutchinson, Yingning Zhang, Mitesh Shridhar, John H Evans, Madison M Buchanan, Tina X Zhao, Peter F Slivka, Benjamen D Coats, Niloofar Rezvani, Julie Wieseler, Travis S Hughes, Kyle E Landgraf, Stefanie Chan, Stephanie Fong, Simon Phipps, Joseph J Falke, Leslie A Leinwand, Steven F Maier, Hang Yin, Kenner C Rice, Linda R Watkins
Opioid-induced proinflammatory glial activation modulates wide-ranging aspects of opioid pharmacology including: opposition of acute and chronic opioid analgesia, opioid analgesic tolerance, opioid-induced hyperalgesia, development of opioid dependence, opioid reward, and opioid respiratory depression. However, the mechanism(s) contributing to opioid-induced proinflammatory actions remains unresolved. The potential involvement of toll-like receptor 4 (TLR4) was examined using in vitro, in vivo, and in silico techniques...
January 2010: Brain, Behavior, and Immunity
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