Interactions between the Nociceptin and Toll-like Receptor Systems.

Abstract

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.

• Authors: Lan Zhang, Ulrike M Stamer, Melody Ying-Yu Huang, Frank Stüber
• Journal: Cells (Cells) Vol. 11 Issue 7 (03 23 2022) ISSN: 2073-4409 [Electronic] Switzerland
• PMID: 35406649 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipopolysaccharides
• Opioid Peptides
• RNA, Messenger
• Toll-Like Receptor 2
• Toll-Like Receptor 4
• Toll-Like Receptor 7
• Toll-Like Receptor 9
• Toll-Like Receptors
• Tetradecanoylphorbol Acetate

Topics

• Humans
• Inflammation
• Lipopolysaccharides (pharmacology)
• Opioid Peptides
• RNA, Messenger (genetics)
• Tetradecanoylphorbol Acetate
• Toll-Like Receptor 2
• Toll-Like Receptor 4
• Toll-Like Receptor 7
• Toll-Like Receptor 9
• Toll-Like Receptors (genetics)
• Nociceptin