Expression und Funktion des ORL-1-Rezeptors auf humanen Leukozyten

Krüger, Christian; Köthe, L.; Struppert, A; Pietruck, Christian; Simm, Andreas; Grond, Stefan

doi:10.1007/s00482-006-0488-1

Cited by 7 publications

(5 citation statements)

References 29 publications

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“…On the other hand, nociceptin mRNA was up-regulated by LPS in rat astrocytes and in mice sensory neuron cultures and NOP expression was strongly induced after activation of human lymphocytes by phytohaemagglutinin [13], [15], [26]. Williams and co-workers [7], [8] reported of NOP and PNoc mRNA expression in human peripheral blood mononuclear cells, whereas other authors described NOP mRNA expression on human granulocytes, lymphocytes and monocytes and nociceptin transcripts in resting human peripheral blood lymphocytes, specifically CD19+ B cells [29], [30].…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Mediators Influence the Expression of Nociceptin and Its Receptor in Human Whole Blood Cultures

2013

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BackgroundNociceptin/orphanin FQ and its receptor (NOP) are involved in immune responses, inflammation and pain processing. The aim of this study was to investigate the modulation of NOP and prepro-nociceptin (PNoc), the precursor of nociceptin, by inflammatory mediators in human whole blood.MethodsPeripheral blood from healthy volunteers was cultured for 0, 3, 6 and 24 hrs with or without lipopolysaccharide (LPS), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-10 or interferon (IFN)-γ. NOP and PNoc mRNA of peripheral white blood cells were detected by quantitative RT-PCR. Cytokine concentrations in supernatants of whole blood cultures were measured using ELISA. In addition, an intervention experiment using anti-cytokine antibodies was conducted to evaluate possible mechanisms involved in the modulation of NOP and PNoc by LPS. The primary goal was to investigate NOP and PNoc mRNA expression in human peripheral blood under inflammatory conditions.ResultsLPS significantly suppressed NOP (median area under the mRNA-expression-time curve (1st/3rd quartile): 5.4 (4.6/6.6) normalized ratio · hr) and PNoc expression (40.8 (34.4/49.5)) compared to baseline measures (NOP: 22.7 (17.1/25.3); PNoc: 69.9 (58.4/89.2), both p<0.001). LPS incubation induced cytokine concentrations (TNF-α, IL-1β, IL-10 and IFN-γ) in whole blood cultures. Incubation with TNF-α, IL-1β, IL-10 or IFN-γ decreased NOP mRNA levels to varying extents (p<0.05 for all). In contrast, PNoc mRNA expression was decreased by IL-10 only (p = 0.018). The LPS effect on NOP expression could be antagonized by anti-TNF-α and anti-IL-1β, whereas anti-IL-10 and anti-INF-γ had no effect. There was no change of PNoc expression when LPS induced cytokines were antagonized by the respective antibodies.ConclusionsLPS as well as cytokines suppress mainly NOP and, in part, PNoc mRNA expression in human whole blood cultures. This may represent a negative feedback loop to the previously described upregulation of cytokines by PNoc.

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Section: Discussionmentioning

confidence: 99%

Inflammatory Mediators Influence the Expression of Nociceptin and Its Receptor in Human Whole Blood Cultures

2013

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“…15 16 The receptor protein was detected on the cell surface of all types of white blood cells without any age-or sex-dependent differences. 17 The existence of NOP on T-cells and the ability of immune cells to produce N/OFQ 5 14 suggest an immunomodulatory role. For pN/OFQ, expression in peripheral blood mononuclear cells and neutrophils has also been described.…”

Section: Discussionmentioning

confidence: 99%

Expression of the nociceptin precursor and nociceptin receptor is modulated in cancer and septic patients

Stamer

Book

Comos

et al. 2011

British Journal of Anaesthesia

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“…NOP‐eGFP knock‐in mice have been used to examine expression‐function but with a neuronal focus (Ozawa et al ., ). Outside the nervous system, we and others have shown the presence of the NOP receptor in immune tissues, but due to presumed ultra‐low expression, this has been suggested through PCR and modulation of immune function (Kruger et al ., ; Zhang et al ., ). While it is possible to obtain acceptable amounts of cerebral tissue to measure opioid expression through radioligand binding, the quantities of peripheral tissue available are most often inadequate for such studies.…”

Section: Introductionmentioning

confidence: 99%

Nociceptin/Orphanin FQ (N/OFQ) conjugated to ATTO594: a novel fluorescent probe for the N/OFQ (NOP) receptor

Bird

Guerrini

Willets

et al. 2018

British J Pharmacology

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Background and PurposeThe nociceptin/orphanin FQ (N/OFQ) receptor (NOP) is a member of the opioid receptor family and is involved in a number of physiological responses, pain and immune regulation as examples. In this study, we conjugated a red fluorophore‐ATTO594 to the peptide ligand N/OFQ (N/OFQATTO594) for the NOP receptor and explored NOP receptor function at high (in recombinant systems) and low (on immune cells) expression.Experimental ApproachWe assessed N/OFQATTO594 receptor binding, selectivity and functional activity in recombinant (CHO) cell lines. Live cell N/OFQATTO594 binding was measured in (i) HEK cells expressing NOP and NOPGFP receptors, (ii) CHO cells expressing the hNOPGαqi5 chimera (to force coupling to measurable Ca2+ responses) and (iii) freshly isolated human polymorphonuclear cells (PMN).Key ResultsN/OFQATTO594 bound to NOP receptor with nM affinity and high selectivity. N/OFQATTO594 activated NOP receptor by reducing cAMP formation and increasing Ca2+ levels in CHOhNOPGαqi5 cells. N/OFQATTO594 was also able to visualize NOP receptors at low expression levels on PMN cells. In NOP‐GFP‐tagged receptors, N/OFQATTO594 was used in a FRET protocol where GFP emission activated ATTO, visualizing ligand–receptor interaction. When the NOPGFP receptor is activated by N/OFQATTO594, movement of ligand and receptor from the cell surface to the cytosol can be measured.Conclusions and ImplicationsIn the absence of validated NOP receptor antibodies and issues surrounding the use of radiolabels (especially in low expression systems), these data indicate the utility of N/OFQATTO594 to study a wide range of N/OFQ‐driven cellular responses.

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Expression und Funktion des ORL-1-Rezeptors auf humanen Leukozyten

Abstract: The ORL-1 receptor is expressed by all subtypes of leukocytes. The function of this receptor is not the modulation of cytokine production and requires further studies.

Cited by 7 publications

References 29 publications

Inflammatory Mediators Influence the Expression of Nociceptin and Its Receptor in Human Whole Blood Cultures

Inflammatory Mediators Influence the Expression of Nociceptin and Its Receptor in Human Whole Blood Cultures

Expression of the nociceptin precursor and nociceptin receptor is modulated in cancer and septic patients

Nociceptin/Orphanin FQ (N/OFQ) conjugated to ATTO594: a novel fluorescent probe for the N/OFQ (NOP) receptor

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