Interactions between the Nociceptin and Toll-like Receptor Systems

• Published in: Cells (Basel, Switzerland) Switzerland), 2022-03, Vol.11 (7), p.1085
• Main Authors: Zhang, Lan, Stamer, Ulrike M, Huang, Melody Ying-Yu, Stüber, Frank
• Format: Article
• Language: English
• Subjects: 12-O-Tetradecanoylphorbol-13-acetate; Acetic acid; Agonists; Antibodies; cell cultures; Cell membranes; Experiments; Flow cytometry; Humans; Imiquimod; Inflammation; Ligands; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Lipoteichoic acid; Monocytes; mRNA; Narcotics; Nociceptin; nociceptin receptor; Oligonucleotides; Opioid Peptides; Opioid receptors; Pain; Proteins; RNA, Messenger - genetics; Tetradecanoylphorbol Acetate; TLR2 protein; TLR4 protein; TLR7 protein; TLR9 protein; Toll-Like Receptor 2; Toll-Like Receptor 4; Toll-Like Receptor 7; Toll-Like Receptor 9; Toll-like receptors; Toll-Like Receptors - genetics
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11071085

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.