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Suppression of CCL2/MCP-1 and CCL5/RANTES expression by nociceptin in human monocytes
David E Kaminsky1, Thomas J Rogers
1Department of Microbiology and Immunology, Center for Substance Abuse Research, Temple University School of Medicine, 3307 N. Broad Street, Philadelphia, PA 19140, USA.
Abstract:
The receptor designated Opioid Receptor-Like 1 (ORL1) is abundantly expressed in the central nervous system (CNS) as well as by cells of the immune system. While much is known about the function of ORL1 in the CNS, there is little information in the literature about the role of ORL1 in the immune response. There have been numerous reports documenting the effects of GPCR activation on the expression of chemokines crucial in mediating inflammatory events in biological systems. The aim of the present work was to examine the effect of nociceptin administration on the pro-inflammatory chemokine expression of human monocytes. We report here that human CD14(+) monocytes expresses the mRNA for ORL1. Our results also demonstrate that nociceptin can suppress the production of CCL2/MCP-1 and CCL5/RANTES chemokine protein in both primary CD14(+) human monocytes and monocyte-like cell lines. However, nociceptin does not appear to regulate the expression of these chemokines at the level of transcription, as CCL2/MCP-1 and CCL5/RANTES mRNA levels following nociceptin treatment of monocytes were essentially normal. Although the mechanism of chemokine regulation by nociceptin is as yet unknown, it is evident that the ORL1/nociceptin system plays a role in regulating chemotactic responses of leukocytes through chemokine suppression. Finally, these data may provide the initial basis for the development of ORL1 agonists and antagonists for therapeutic treatment of inflammatory disease.
Insights
The Opioid Receptor-Like 1 (ORL1) system in human monocytes suppresses inflammatory chemokine production. Nociceptin, an ORL1 ligand, reduces chemokine protein but not mRNA, suggesting post-transcriptional regulation in immune responses.
Area of Science:
- Immunology
- Neuroscience
- Pharmacology
Background:
- Opioid Receptor-Like 1 (ORL1) is expressed in the central nervous system and immune cells.
- The role of ORL1 in immune responses, particularly chemokine expression, is largely unknown.
- G protein-coupled receptor (GPCR) activation influences chemokine expression, impacting inflammation.
Purpose of the Study:
- To investigate the effect of nociceptin on pro-inflammatory chemokine expression in human monocytes.
- To determine if ORL1 signaling modulates chemokine production in immune cells.
Main Methods:
- Human CD14(+) monocytes and monocyte-like cell lines were used.
- Nociceptin administration was employed to assess its impact.
- Quantitative analysis of chemokine mRNA and protein levels (CCL2/MCP-1, CCL5/RANTES) was performed.
Main Results:
- Human monocytes express ORL1 mRNA.
- Nociceptin significantly suppressed the protein production of CCL2/MCP-1 and CCL5/RANTES.
- Nociceptin did not alter the mRNA levels of these chemokines, indicating post-transcriptional regulation.
Conclusions:
- The ORL1/nociceptin system plays a role in regulating leukocyte chemotaxis via chemokine suppression.
- These findings suggest potential therapeutic applications for ORL1 agonists/antagonists in inflammatory diseases.
