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; Stamer, Ulrike (2019). ERK and p38 contribute to the regulation of nociceptin and the nociceptin receptor in human peripheral blood leukocytes. Molecular pain, 15, p. 1744806919828921. Sage 10.1177/1744806919828921

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic and Policlinic for Anaesthesiology and Pain Therapy
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Anästhesiologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Anästhesiologie

UniBE Contributor:

Zhang, Lan; Stüber, Frank; Lippuner, Christoph and Stamer, Ulrike

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1744-8069

Publisher:

Sage

Language:

English

Submitter:

Jeannie Wurz

Date Deposited:

15 Jul 2019 11:12

Last Modified:

21 Jul 2019 02:39

Publisher DOI:

10.1177/1744806919828921

PubMed ID:

30665329

Uncontrolled Keywords:

Leukocytes nociceptin nociceptin receptor phorbol-12-myristate signal transduction

BORIS DOI:

10.7892/boris.130329

URI:

https://boris.unibe.ch/id/eprint/130329

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