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Interactions between the Nociceptin and Toll-like Receptor Systems.
Lan Zhang1,2, Ulrike M Stamer1,2, Melody Ying-Yu Huang1,2
1Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.
Cells
|April 12, 2022
Summary
Nociceptin and toll-like receptors (TLRs) interact, with nociceptin showing anti-inflammatory effects in monocytes. This study reveals that nociceptin suppresses TLRs, suggesting a role in modulating inflammatory responses.
Area of Science:
- Immunology
- Neuroscience
- Pharmacology
Background:
- Nociceptin/nociceptin receptor (NOP) system is implicated in pain and inflammation.
- Toll-like receptors (TLRs) are crucial in inflammation and influence opioid systems.
- Interactions between nociceptin and TLRs are not fully understood.
Purpose of the Study:
- To investigate the interactions between the nociceptin system and toll-like receptors (TLRs).
- To determine the role of nociceptin in modulating TLR expression and function in human monocytes.
Main Methods:
- Human THP-1 cells were stimulated with phorbol myristate acetate (PMA) and various TLR agonists (LTA, LPS, IMQ, ODN).
- Gene and protein expression of prepronociceptin (ppNOC), NOP, and TLRs were quantified using RT-qPCR and flow cytometry.
- Cells were also treated with nociceptin to assess its effects on TLRs.
Main Results:
- PMA upregulated ppNOC mRNA, intracellular nociceptin, and NOP protein.
- Certain TLR agonists (LTA, LPS, IMQ, ODN) modulated PMA's effects on ppNOC and NOP.
- Nociceptin dose-dependently suppressed TLR2, TLR4, TLR7, and TLR9 protein expression.
- PMA, LPS, IMQ, and ODN increased NOP protein levels.
Conclusions:
- The nociceptin system exhibits anti-inflammatory properties in monocytes.
- Antagonistic interactions between nociceptin and TLRs suggest a regulatory role in inflammation.
- Targeting the nociceptin system may offer therapeutic strategies for inflammatory conditions.
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