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Interactions between the Nociceptin and Toll-like Receptor Systems

Nociceptin and the nociceptin receptor (NOP) have been described as targets for treatment of pain and inflammation, whereas toll-like receptors (TLRs) play key roles in inflammation and impact opioid receptors and endogenous opioids expression. In this study, interactions between the nociceptin and...

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Autores principales: Zhang, Lan, Stamer, Ulrike M., Huang, Melody Ying-Yu, Stüber, Frank
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8997556/
https://www.ncbi.nlm.nih.gov/pubmed/35406649
http://dx.doi.org/10.3390/cells11071085
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author Zhang, Lan
Stamer, Ulrike M.
Huang, Melody Ying-Yu
Stüber, Frank
author_facet Zhang, Lan
Stamer, Ulrike M.
Huang, Melody Ying-Yu
Stüber, Frank
author_sort Zhang, Lan
collection PubMed
description Nociceptin and the nociceptin receptor (NOP) have been described as targets for treatment of pain and inflammation, whereas toll-like receptors (TLRs) play key roles in inflammation and impact opioid receptors and endogenous opioids expression. In this study, interactions between the nociceptin and TLR systems were investigated. Human THP-1 cells were cultured with or without phorbol myristate acetate (PMA 5 ng/mL), agonists specific for TLR2 (lipoteichoic acid, LTA 10 µg/mL), TLR4 (lipopolysaccharide, LPS 100 ng/mL), TLR7 (imiquimod, IMQ 10 µg/mL), TLR9 (oligonucleotide (ODN) 2216 1 µM), PMA+TLR agonists, or nociceptin (0.01–100 nM). Prepronociceptin (ppNOC), NOP, and TLR mRNAs were quantified by RT-qPCR. Proteins were measured using flow cytometry. PMA upregulated ppNOC mRNA, intracellular nociceptin, and cell membrane NOP proteins (all p < 0.05). LTA and LPS prevented PMA’s upregulating effects on ppNOC mRNA and nociceptin protein (both p < 0.05). IMQ and ODN 2216 attenuated PMA’s effects on ppNOC mRNA. PMA, LPS, IMQ, and ODN 2216 increased NOP protein levels (all p < 0.05). PMA+TLR agonists had no effects on NOP compared to PMA controls. Nociceptin dose-dependently suppressed TLR2, TLR4, TLR7, and TLR9 proteins (all p < 0.01). Antagonistic effects observed between the nociceptin and TLR systems suggest that the nociceptin system plays an anti-inflammatory role in monocytes under inflammatory conditions.
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spelling pubmed-89975562022-04-12 Interactions between the Nociceptin and Toll-like Receptor Systems Zhang, Lan Stamer, Ulrike M. Huang, Melody Ying-Yu Stüber, Frank Cells Article Nociceptin and the nociceptin receptor (NOP) have been described as targets for treatment of pain and inflammation, whereas toll-like receptors (TLRs) play key roles in inflammation and impact opioid receptors and endogenous opioids expression. In this study, interactions between the nociceptin and TLR systems were investigated. Human THP-1 cells were cultured with or without phorbol myristate acetate (PMA 5 ng/mL), agonists specific for TLR2 (lipoteichoic acid, LTA 10 µg/mL), TLR4 (lipopolysaccharide, LPS 100 ng/mL), TLR7 (imiquimod, IMQ 10 µg/mL), TLR9 (oligonucleotide (ODN) 2216 1 µM), PMA+TLR agonists, or nociceptin (0.01–100 nM). Prepronociceptin (ppNOC), NOP, and TLR mRNAs were quantified by RT-qPCR. Proteins were measured using flow cytometry. PMA upregulated ppNOC mRNA, intracellular nociceptin, and cell membrane NOP proteins (all p < 0.05). LTA and LPS prevented PMA’s upregulating effects on ppNOC mRNA and nociceptin protein (both p < 0.05). IMQ and ODN 2216 attenuated PMA’s effects on ppNOC mRNA. PMA, LPS, IMQ, and ODN 2216 increased NOP protein levels (all p < 0.05). PMA+TLR agonists had no effects on NOP compared to PMA controls. Nociceptin dose-dependently suppressed TLR2, TLR4, TLR7, and TLR9 proteins (all p < 0.01). Antagonistic effects observed between the nociceptin and TLR systems suggest that the nociceptin system plays an anti-inflammatory role in monocytes under inflammatory conditions. MDPI 2022-03-23 /pmc/articles/PMC8997556/ /pubmed/35406649 http://dx.doi.org/10.3390/cells11071085 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Lan
Stamer, Ulrike M.
Huang, Melody Ying-Yu
Stüber, Frank
Interactions between the Nociceptin and Toll-like Receptor Systems
title Interactions between the Nociceptin and Toll-like Receptor Systems
title_full Interactions between the Nociceptin and Toll-like Receptor Systems
title_fullStr Interactions between the Nociceptin and Toll-like Receptor Systems
title_full_unstemmed Interactions between the Nociceptin and Toll-like Receptor Systems
title_short Interactions between the Nociceptin and Toll-like Receptor Systems
title_sort interactions between the nociceptin and toll-like receptor systems
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8997556/
https://www.ncbi.nlm.nih.gov/pubmed/35406649
http://dx.doi.org/10.3390/cells11071085
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