Inducible Expression of Functional Mu Opioid Receptors in Murine Dendritic Cells

Overview

Journal J Neuroimmune Pharmacol

Specialties Allergy & Immunology
Neurology
Pharmacology

Date 2009 Feb 4

PMID 19189219

Citations 15

Authors

Zheng-Hong Li

Niansheng Chu

Li-Dong Shan

Shan Gong

Qi-Zhang Yin

Xing-Hong Jiang

Affiliations

Soon will be listed here.

Abstract

Opioids are known to exert direct effects on the immune system, and the expression of functional opioid receptors has been reported on several immune cell types. Dendritic cells (DCs) are important inducers and regulators of immune responses. In this study, we investigated whether murine dendritic cells express functional mu opioid receptors (MOR). RT-PCR analysis and double immunofluorescence staining revealed the expression of MOR in activated murine dendritic cells. We also studied the dynamic expression of MOR messenger RNA in murine dendritic cells in response to different Toll-like receptor ligands. Functionally, treatment of DCs with endomorphin 1 (EM1), a specific agonist of MOR, can inhibit the forskolin-induced formation of cyclic adenosine monophosphate level in activated DCs. Moreover, EM1 treatment resulted in less activation of p38 MAPK and more activation of ERK signaling in lipopolysaccharide-stimulated DCs. Consistently, treatment of DCs with EM1 altered cytokine production by increasing IL-10 and decreasing IL-12 and IL-23. Our results suggest that MOR is inducibly expressed on activated DCs and functionally mediates EM1-induced effects on DCs. Thus, dendritic cells might be involved in crosstalk between the neuroendocrine and the immune system.

Citing Articles

The aetiology of social deficits within mental health disorders: The role of the immune system and endogenous opioids.

Charles S, Farias M, Dunbar R Brain Behav Immun Health. 2024; 1:100003.

PMID: 38377411 PMC: 8474498. DOI: 10.1016/j.bbih.2019.100003.

Knowledge Mapping of Opioids and Immunomodulation: A Bibliometric Analysis (2000-2022).

Subinuer Kurexi , Wang K, Chen T J Pain Res. 2023; 16:1499-1515.

PMID: 37179815 PMC: 10171226. DOI: 10.2147/JPR.S401326.

Multiple Sclerosis and the Endogenous Opioid System.

Dworsky-Fried Z, Chadwick C, Kerr B, Taylor A Front Neurosci. 2021; 15:741503.

PMID: 34602975 PMC: 8484329. DOI: 10.3389/fnins.2021.741503.

A Systematic Review of Opioid Use Disorder and Related Biomarkers.

Bryant B, Eaton E, Li L Front Psychiatry. 2021; 12:708283.

PMID: 34456765 PMC: 8385272. DOI: 10.3389/fpsyt.2021.708283.

In schizophrenia, non-remitters and partial remitters to treatment with antipsychotics are qualitatively distinct classes with respect to neurocognitive deficits and neuro-immune biomarkers: results of soft independent modeling of class analogy.

Al-Hakeim H, Mousa R, Al-Dujaili A, Maes M Metab Brain Dis. 2021; 36(5):939-955.

PMID: 33580860 DOI: 10.1007/s11011-021-00685-9.

References

Roy S, Cain K, Chapin R, Charboneau R, Barke R . Morphine modulates NF kappa B activation in macrophages. Biochem Biophys Res Commun. 1998; 245(2):392-6. DOI: 10.1006/bbrc.1998.8415. View

Frassdorf J, Weber N, Obal D, Toma O, Mullenheim J, Kojda G . Morphine induces late cardioprotection in rat hearts in vivo: the involvement of opioid receptors and nuclear transcription factor kappaB. Anesth Analg. 2005; 101(4):934-941. DOI: 10.1213/01.ane.0000172130.70274.84. View

Qian C, Jiang X, An H, Yu Y, Guo Z, Liu S . TLR agonists promote ERK-mediated preferential IL-10 production of regulatory dendritic cells (diffDCs), leading to NK-cell activation. Blood. 2006; 108(7):2307-15. DOI: 10.1182/blood-2006-03-005595. View

Borner C, Kraus J, Schroder H, Ammer H, Hollt V . Transcriptional regulation of the human mu-opioid receptor gene by interleukin-6. Mol Pharmacol. 2004; 66(6):1719-26. DOI: 10.1124/mol.104.003806. View

Rutella S, Danese S, Leone G . Tolerogenic dendritic cells: cytokine modulation comes of age. Blood. 2006; 108(5):1435-40. DOI: 10.1182/blood-2006-03-006403. View

Bussiere J, Adler M, Rogers T, Eisenstein T . Cytokine reversal of morphine-induced suppression of the antibody response. J Pharmacol Exp Ther. 1993; 264(2):591-7. View

Chang S, Beltran J, Swarup S . Expression of the mu opioid receptor in the human immunodeficiency virus type 1 transgenic rat model. J Virol. 2007; 81(16):8406-11. PMC: 1951376. DOI: 10.1128/JVI.00155-07. View

Friedman H, Newton C, Klein T . Microbial infections, immunomodulation, and drugs of abuse. Clin Microbiol Rev. 2003; 16(2):209-19. PMC: 153143. DOI: 10.1128/CMR.16.2.209-219.2003. View

McCarthy L, Wetzel M, Sliker J, Eisenstein T, Rogers T . Opioids, opioid receptors, and the immune response. Drug Alcohol Depend. 2001; 62(2):111-23. DOI: 10.1016/s0376-8716(00)00181-2. View

10.

Rozenfeld-Granot G, Toren A, Amariglio N, Nagler A, Rosenthal E, Biniaminov M . MAP kinase activation by mu opioid receptor in cord blood CD34(+)CD38(-) cells. Exp Hematol. 2002; 30(5):473-80. DOI: 10.1016/s0301-472x(02)00786-5. View

11.

Borner C, Kraus J, Bedini A, Schraven B, Hollt V . T-cell receptor/CD28-mediated activation of human T lymphocytes induces expression of functional mu-opioid receptors. Mol Pharmacol. 2008; 74(2):496-504. DOI: 10.1124/mol.108.046029. View

12.

Yi A, Yoon J, Yeo S, Hong S, English B, Krieg A . Role of mitogen-activated protein kinases in CpG DNA-mediated IL-10 and IL-12 production: central role of extracellular signal-regulated kinase in the negative feedback loop of the CpG DNA-mediated Th1 response. J Immunol. 2002; 168(9):4711-20. DOI: 10.4049/jimmunol.168.9.4711. View

13.

Belcheva M, Haas P, Tan Y, Heaton V, Coscia C . The fibroblast growth factor receptor is at the site of convergence between mu-opioid receptor and growth factor signaling pathways in rat C6 glioma cells. J Pharmacol Exp Ther. 2002; 303(3):909-18. DOI: 10.1124/jpet.102.038554. View

14.

Azuma Y, Ohura K . Endomorphins 1 and 2 inhibit IL-10 and IL-12 production and innate immune functions, and potentiate NF-kappaB DNA binding in THP-1 differentiated to macrophage-like cells. Scand J Immunol. 2002; 56(3):260-9. DOI: 10.1046/j.1365-3083.2002.01128.x. View

15.

Bidlack J, Khimich M, Parkhill A, Sumagin S, Sun B, Tipton C . Opioid receptors and signaling on cells from the immune system. J Neuroimmune Pharmacol. 2007; 1(3):260-9. DOI: 10.1007/s11481-006-9026-2. View

16.

Vigano D, Rubino T, Di Chiara G, Ascari I, Massi P, Parolaro D . Mu opioid receptor signaling in morphine sensitization. Neuroscience. 2003; 117(4):921-9. DOI: 10.1016/s0306-4522(02)00825-4. View

17.

Husted T, Govindaswami M, Oeltgen P, Rudich S, Lentsch A . A delta2-opioid agonist inhibits p38 MAPK and suppresses activation of murine macrophages. J Surg Res. 2005; 128(1):45-9. DOI: 10.1016/j.jss.2005.04.003. View

18.

Dalpke A, Heeg K . Signal integration following Toll-like receptor triggering. Crit Rev Immunol. 2002; 22(3):217-50. View

19.

Ghiringhelli F, Apetoh L, Housseau F, Kroemer G, Zitvogel L . Links between innate and cognate tumor immunity. Curr Opin Immunol. 2007; 19(2):224-31. DOI: 10.1016/j.coi.2007.02.003. View

20.

Roy S, Wang J, Kelschenbach J, Koodie L, Martin J . Modulation of immune function by morphine: implications for susceptibility to infection. J Neuroimmune Pharmacol. 2007; 1(1):77-89. DOI: 10.1007/s11481-005-9009-8. View