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The influence of methadone on toll‐like receptor 4 and human mu opioid receptor expression
Author(s) -
Dodson Summer,
Das Subhas,
Davis Randall,
Stevens Craig W.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1175.9
Subject(s) - tlr4 , methadone , receptor , toll like receptor , opioid , lipopolysaccharide , opioid receptor , immune system , medicine , pharmacology , methadone maintenance , inflammation , immunology , chemistry , innate immune system
This research discusses the potential interaction of toll‐like receptor 4 (TLR4), an innate immune receptor found both peripherally and in the CNS, and the human mu opioid receptor (hMOR) in the presence of methadone and/or lipopolysaccharide (LPS). Opioid dependency increases the likelihood of infection and inflammation and studies have found that methadone maintenance programs yeild improved immune function in participants. This well documented immunologic dysfunction of opioid dependent individuals has led to the investigation into the role of TLR4 in this system. It is important to include the effects of methadone both alone and in the presence of LPS due to opportunistic infection in abusers. HEK Blue 4 cells overexpressing TLR4 protein have been used in this research primarily as a tool to identify TLR4 activity. 100 μM methadone significantly inhibits TLR4 activation in the presence of 100 ng/mL LPS. Methadone at 100 μM (+/− LPS) upregulates hMOR transcript in this cell line. CHME‐5 microglial cells also show a link between methadone and TLR4 mRNA expression. 10 μM methadone increases TLR4 mRNA after 30 minutes. 100 μM methadone with LPS has higher expression at 30 minutes then declines. This research begins to illustrate the complex relationship of TLR4 and methadone in neuroimmunomodulation. Supported in part by an Oklahoma Center for the Advancement of Science and Technology (OCAST) HR10–31 to CWS.