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ERK and p38 contribute to the regulation of nociceptin and the nociceptin receptor in human peripheral blood leukocytes

Little is known about the mechanisms involved in the regulation of nociceptin and its receptor (nociceptin opioid peptide receptor, NOP) in response to inflammation and pain in humans. In this study, specific signaling pathways contributing to the regulation of nociceptin and NOP in human peripheral...

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Autores principales: Zhang, Lan, Stüber, Frank, Lippuner, Christoph, Schiff, Marcel, M Stamer, Ulrike
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378488/
https://www.ncbi.nlm.nih.gov/pubmed/30665329
http://dx.doi.org/10.1177/1744806919828921
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author Zhang, Lan
Stüber, Frank
Lippuner, Christoph
Schiff, Marcel
M Stamer, Ulrike
author_facet Zhang, Lan
Stüber, Frank
Lippuner, Christoph
Schiff, Marcel
M Stamer, Ulrike
author_sort Zhang, Lan
collection PubMed
description Little is known about the mechanisms involved in the regulation of nociceptin and its receptor (nociceptin opioid peptide receptor, NOP) in response to inflammation and pain in humans. In this study, specific signaling pathways contributing to the regulation of nociceptin and NOP in human peripheral blood leukocytes were investigated. After approval by the ethics committee, peripheral blood obtained from healthy donors was cultured with or without phorbol-12-myristate-13-acetate (PMA). Prepronociceptin (ppNOC) and NOP mRNA were analyzed by real-time quantitative polymerase chain reaction, and nociceptin concentrations in culture supernatants by fluorescent enzyme immunoassay. Nociceptin and NOP protein levels in blood leukocyte subsets were determined using flow cytometry. To examine the contribution of signaling pathways to ppNOC and NOP regulation, blood was pre-treated with kinase inhibitors specific for ERK, JNK, p38, and NFκB pathways prior to culturing with or without PMA. PMA dose-dependently upregulated ppNOC mRNA but downregulated NOP mRNA in human peripheral blood leukocytes. PMA 10 ng/ml increased ppNOC after 6 h and suppressed NOP after 3 h compared to controls (both P <0.005). Nociceptin concentrations were increased in supernatants of PMA-induced blood samples after 24 h (P <0.005), whereas expression of cell-membrane NOP was decreased by PMA in blood leukocyte subsets (all P <0.05). Blockade of ERK or p38 pathways partially prevented PMA effects on ppNOC and NOP mRNA (all P <0.05). The combination of ERK and p38 inhibitors completely reversed the effects of PMA (P <0.05). ERK and p38 are two major signaling pathways regulating nociceptin and its receptor in human peripheral blood leukocytes under inflammatory conditions.
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spelling pubmed-63784882019-02-22 ERK and p38 contribute to the regulation of nociceptin and the nociceptin receptor in human peripheral blood leukocytes Zhang, Lan Stüber, Frank Lippuner, Christoph Schiff, Marcel M Stamer, Ulrike Mol Pain Research Article Little is known about the mechanisms involved in the regulation of nociceptin and its receptor (nociceptin opioid peptide receptor, NOP) in response to inflammation and pain in humans. In this study, specific signaling pathways contributing to the regulation of nociceptin and NOP in human peripheral blood leukocytes were investigated. After approval by the ethics committee, peripheral blood obtained from healthy donors was cultured with or without phorbol-12-myristate-13-acetate (PMA). Prepronociceptin (ppNOC) and NOP mRNA were analyzed by real-time quantitative polymerase chain reaction, and nociceptin concentrations in culture supernatants by fluorescent enzyme immunoassay. Nociceptin and NOP protein levels in blood leukocyte subsets were determined using flow cytometry. To examine the contribution of signaling pathways to ppNOC and NOP regulation, blood was pre-treated with kinase inhibitors specific for ERK, JNK, p38, and NFκB pathways prior to culturing with or without PMA. PMA dose-dependently upregulated ppNOC mRNA but downregulated NOP mRNA in human peripheral blood leukocytes. PMA 10 ng/ml increased ppNOC after 6 h and suppressed NOP after 3 h compared to controls (both P <0.005). Nociceptin concentrations were increased in supernatants of PMA-induced blood samples after 24 h (P <0.005), whereas expression of cell-membrane NOP was decreased by PMA in blood leukocyte subsets (all P <0.05). Blockade of ERK or p38 pathways partially prevented PMA effects on ppNOC and NOP mRNA (all P <0.05). The combination of ERK and p38 inhibitors completely reversed the effects of PMA (P <0.05). ERK and p38 are two major signaling pathways regulating nociceptin and its receptor in human peripheral blood leukocytes under inflammatory conditions. SAGE Publications 2019-02-13 /pmc/articles/PMC6378488/ /pubmed/30665329 http://dx.doi.org/10.1177/1744806919828921 Text en © The Author(s) 2019 http://creativecommons.org/licenses/by-nc/4.0/ Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Research Article
Zhang, Lan
Stüber, Frank
Lippuner, Christoph
Schiff, Marcel
M Stamer, Ulrike
ERK and p38 contribute to the regulation of nociceptin and the nociceptin receptor in human peripheral blood leukocytes
title ERK and p38 contribute to the regulation of nociceptin and the nociceptin receptor in human peripheral blood leukocytes
title_full ERK and p38 contribute to the regulation of nociceptin and the nociceptin receptor in human peripheral blood leukocytes
title_fullStr ERK and p38 contribute to the regulation of nociceptin and the nociceptin receptor in human peripheral blood leukocytes
title_full_unstemmed ERK and p38 contribute to the regulation of nociceptin and the nociceptin receptor in human peripheral blood leukocytes
title_short ERK and p38 contribute to the regulation of nociceptin and the nociceptin receptor in human peripheral blood leukocytes
title_sort erk and p38 contribute to the regulation of nociceptin and the nociceptin receptor in human peripheral blood leukocytes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378488/
https://www.ncbi.nlm.nih.gov/pubmed/30665329
http://dx.doi.org/10.1177/1744806919828921
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