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- W3201064314 abstract "In addition to numerous neurological effects,opioids also elicit responses from the immune system. Effects ofopioids have been seen on a variety of immune cell types; however,studies have been unable to fully analyze the expression of opioidreceptors on human immune cells. Individual genetic variability,lack of specific antibodies for opioid receptors, low density ofreceptors on immune cells, and expression of receptors only onsmall subsets of immune cells all hinder the detection of opioidreceptors in the immune system. In addition, some studies havepointed to detectable levels of opioid receptors being present inimmune cells only after induction by cytokine/chemokinestimulation. Preliminary data strongly suggested the presence ofthe kappa opioid receptor on a human monocyte cell line, U-937.This study aimed to verify the presence of this receptor and tofurther characterize the regulation of its expression afterexposure to inflammatory stimuli. RT-PCR analysis showed thatexposure to a bacterial endotoxin, lipopolysaccharide, induced a4-fold increase in KOR mRNA in the U-937 cell line. Furtherinvestigation revealed that this induction was mediated byautocrine/paracrine effects due to the release of the cytokine,interferon-γ. Based on past studies in murine mononuclearleukocytes, this study also hypothesized that KOR activation in theU-937 cell line would lead to inhibition of pro-inflammatorycytokine production. It was observed that κ-selective agonistsinhibited production of TNF-α by impeding NFκB activation. Theseeffects were blocked by the κ-selective antagonist,nor-binaltorphimine. This study presents the first directevidence for regulation of KOR transcripts by cytokines/chemokinesand the first direct functional support for its presence on humanmonocytes. The characterization of the KOR in the U-937 cell lineprovides a useful model for studies on the effects of opioids inperipheral inflammation and gives insight into mechanisms behindneuroinflammatory diseases. The results of this study also aid inunderstanding the multifaceted circumstances that determine opioidreceptor expression on cells of the immune system." @default.
- W3201064314 created "2021-09-27" @default.
- W3201064314 creator A5076803080 @default.
- W3201064314 date "2009-01-01" @default.
- W3201064314 modified "2023-09-23" @default.
- W3201064314 title "Cytokine-mediated regulation of kappa opioid receptorexpression and a role for kappa agonists in inflammation" @default.
- W3201064314 hasPublicationYear "2009" @default.
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