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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| Format: | Article |
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MDPI AG
2022-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/7/1085 |
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| author | Lan Zhang Ulrike M. Stamer Melody Ying-Yu Huang Frank Stüber |
| author_facet | Lan Zhang Ulrike M. Stamer Melody Ying-Yu Huang Frank Stüber |
| author_sort | Lan Zhang |
| collection | DOAJ |
| 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 (<i>ppNOC</i>), <i>NOP</i>, and <i>TLR</i> mRNAs were quantified by RT-qPCR. Proteins were measured using flow cytometry. PMA upregulated <i>ppNOC</i> mRNA, intracellular nociceptin, and cell membrane NOP proteins (all <i>p</i> < 0.05). LTA and LPS prevented PMA’s upregulating effects on <i>ppNOC</i> mRNA and nociceptin protein (both <i>p</i> < 0.05). IMQ and ODN 2216 attenuated PMA’s effects on <i>ppNOC</i> mRNA. PMA, LPS, IMQ, and ODN 2216 increased NOP protein levels (all <i>p</i> < 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 <i>p</i> < 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. |
| first_indexed | 2024-03-09T12:01:47Z |
| format | Article |
| id | doaj.art-8ae80c96810d4755be08d3dcbe94c546 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T12:01:47Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-8ae80c96810d4755be08d3dcbe94c5462023-11-30T23:03:17ZengMDPI AGCells2073-44092022-03-01117108510.3390/cells11071085Interactions between the Nociceptin and Toll-like Receptor SystemsLan Zhang0Ulrike M. Stamer1Melody Ying-Yu Huang2Frank Stüber3Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, SwitzerlandDepartment of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, SwitzerlandDepartment of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, SwitzerlandDepartment of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, SwitzerlandNociceptin 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 (<i>ppNOC</i>), <i>NOP</i>, and <i>TLR</i> mRNAs were quantified by RT-qPCR. Proteins were measured using flow cytometry. PMA upregulated <i>ppNOC</i> mRNA, intracellular nociceptin, and cell membrane NOP proteins (all <i>p</i> < 0.05). LTA and LPS prevented PMA’s upregulating effects on <i>ppNOC</i> mRNA and nociceptin protein (both <i>p</i> < 0.05). IMQ and ODN 2216 attenuated PMA’s effects on <i>ppNOC</i> mRNA. PMA, LPS, IMQ, and ODN 2216 increased NOP protein levels (all <i>p</i> < 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 <i>p</i> < 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.https://www.mdpi.com/2073-4409/11/7/1085cell culturesinflammationnociceptinnociceptin receptorpaintoll-like receptors |
| spellingShingle | Lan Zhang Ulrike M. Stamer Melody Ying-Yu Huang Frank Stüber Interactions between the Nociceptin and Toll-like Receptor Systems Cells cell cultures inflammation nociceptin nociceptin receptor pain toll-like receptors |
| 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 | cell cultures inflammation nociceptin nociceptin receptor pain toll-like receptors |
| url | https://www.mdpi.com/2073-4409/11/7/1085 |
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