Phorbol-12-myristate-13-acetate induces nociceptin in human Mono Mac 6 cells via multiple transduction signalling pathways.

Zhang, Lan; Stuber, Frank; Lippuner, Christoph; Schiff, Marcel; Stamer, Ulrike (2016). Phorbol-12-myristate-13-acetate induces nociceptin in human Mono Mac 6 cells via multiple transduction signalling pathways. British journal of anaesthesia, 117(2), aew063. Oxford University Press 10.1093/bja/aew063

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BACKGROUND

Nociceptin in the peripheral circulation has been proposed to have an immunoregulatory role with regards to inflammation and pain. However, the mechanisms involved in its regulation are still not clear. The aim of this study was to investigate signalling pathways contributing to the regulation of the expression of nociceptin under inflammatory conditions.

METHODS

Mono Mac 6 cells (MM6) were cultured with or without phorbol-12-myristate-13-acetate (PMA). Prepronociceptin (ppNOC) mRNA was detected by RT-qPCR and extracellular nociceptin by fluorescent-enzyme immunoassay. Intracellular nociceptin and phosphorylated kinases were measured using flow cytometry. To evaluate the contribution of various signalling pathways to the regulation of ppNOC mRNA and nociceptin protein, cells were pre-treated with specific kinase inhibitors before co-culturing with PMA.

RESULTS

ppNOC mRNA was expressed in untreated MM6 at low concentrations. Exposure of cells to PMA upregulated ppNOC after nine h compared with controls without PMA (median normalized ratio with IQR: 0.18 (0.15-0.26) vs. 0 (0-0.02), P<0.01). Inhibition of mitogen-activated protein kinases specific for signal transduction reversed the PMA effects (all P<0.001). Induction of nociceptin protein concentrations in PMA stimulated MM6 was prevented predominantly by identity of ERK inhibitor (P<0.05).

CONCLUSIONS

Upregulation of nociceptin expression by PMA in MM6 cells involves several pathways. Underlying mechanisms involved in nociceptin expression may lead to new insights in the treatment of pain and inflammatory diseases.

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, Schiff, Marcel, Stamer, Ulrike

Subjects:

 600 Technology > 610 Medicine & health

ISSN:

 0007-0912

Publisher:

 Oxford University Press

Language:

 English

Submitter:

 Jeannie Wurz

Date Deposited:

 12 Jul 2016 08:53

Last Modified:

 27 Mar 2023 15:08

Publisher DOI:

 10.1093/bja/aew063

PubMed ID:

 27307289

Uncontrolled Keywords:

 RNA, messenger; monocytes; nociceptin; phorbol-12-myristate; signal transduction

BORIS DOI:

 10.7892/boris.83837

URI:

 https://boris.unibe.ch/id/eprint/83837

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