Immunomodulatory Effects of Dopamine in Inflammatory Diseases

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Apr 26

PMID 33897712

Citations 33

Authors

Yifei Feng

Yan Lu

Affiliations

Soon will be listed here.

Abstract

Dopamine (DA) receptor, a significant G protein-coupled receptor, is classified into two families: D1-like (D1 and D5) and D2-like (D2, D3, and D4) receptor families, with further formation of homodimers, heteromers, and receptor mosaic. Increasing evidence suggests that the immune system can be affected by the nervous system and neurotransmitters, such as dopamine. Recently, the role of the DA receptor in inflammation has been widely studied, mainly focusing on NLRP3 inflammasome, NF-κB pathway, and immune cells. This article provides a brief review of the structures, functions, and signaling pathways of DA receptors and their relationships with inflammation. With detailed descriptions of their roles in Parkinson disease, inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis, this article provides a theoretical basis for drug development targeting DA receptors in inflammatory diseases.

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References

Jafari M, Ahangari G, Saberi M, Samangoui S, Torabi R, Zouali M . Distorted expression of dopamine receptor genes in systemic lupus erythematosus. Immunobiology. 2012; 218(7):979-83. DOI: 10.1016/j.imbio.2012.11.002. View

Benitez A, Edens H, Fishman J, Moran K, Asgharnejad M . Rotigotine transdermal system: developing continuous dopaminergic delivery to treat Parkinson's disease and restless legs syndrome. Ann N Y Acad Sci. 2014; 1329:45-66. DOI: 10.1111/nyas.12508. View

Boyle W, Simonet W, Lacey D . Osteoclast differentiation and activation. Nature. 2003; 423(6937):337-42. DOI: 10.1038/nature01658. View

Barcia C, Ros C, Annese V, Gomez A, Ros-Bernal F, Aguado-Llera D . IFN-γ signaling, with the synergistic contribution of TNF-α, mediates cell specific microglial and astroglial activation in experimental models of Parkinson's disease. Cell Death Dis. 2012; 3:e379. PMC: 3434670. DOI: 10.1038/cddis.2012.123. View

Levite M . Dopamine and T cells: dopamine receptors and potent effects on T cells, dopamine production in T cells, and abnormalities in the dopaminergic system in T cells in autoimmune, neurological and psychiatric diseases. Acta Physiol (Oxf). 2015; 216(1):42-89. DOI: 10.1111/apha.12476. View

Gonzalez S, Rangel-Barajas C, Peper M, Lorenzo R, Moreno E, Ciruela F . Dopamine D4 receptor, but not the ADHD-associated D4.7 variant, forms functional heteromers with the dopamine D2S receptor in the brain. Mol Psychiatry. 2011; 17(6):650-62. PMC: 3219836. DOI: 10.1038/mp.2011.93. View

Nolan R, Muir R, Runner K, Haddad E, Gaskill P . Role of Macrophage Dopamine Receptors in Mediating Cytokine Production: Implications for Neuroinflammation in the Context of HIV-Associated Neurocognitive Disorders. J Neuroimmune Pharmacol. 2018; 14(1):134-156. PMC: 6391172. DOI: 10.1007/s11481-018-9825-2. View

Guitart X, Moreno E, Rea W, Sanchez-Soto M, Cai N, Quiroz C . Biased G Protein-Independent Signaling of Dopamine D-D Receptor Heteromers in the Nucleus Accumbens. Mol Neurobiol. 2019; 56(10):6756-6769. PMC: 6728209. DOI: 10.1007/s12035-019-1564-8. View

Bonaventura J, Navarro G, Casado-Anguera V, Azdad K, Rea W, Moreno E . Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer. Proc Natl Acad Sci U S A. 2015; 112(27):E3609-18. PMC: 4500251. DOI: 10.1073/pnas.1507704112. View

10.

Capellino S, Cosentino M, Luini A, Bombelli R, Lowin T, Cutolo M . Increased expression of dopamine receptors in synovial fibroblasts from patients with rheumatoid arthritis: inhibitory effects of dopamine on interleukin-8 and interleukin-6. Arthritis Rheumatol. 2014; 66(10):2685-93. DOI: 10.1002/art.38746. View

11.

Castro-Hernandez J, Afonso-Oramas D, Cruz-Muros I, Salas-Hernandez J, Barroso-Chinea P, Moratalla R . Prolonged treatment with pramipexole promotes physical interaction of striatal dopamine D3 autoreceptors with dopamine transporters to reduce dopamine uptake. Neurobiol Dis. 2014; 74:325-35. DOI: 10.1016/j.nbd.2014.12.007. View

12.

Nagai Y, Ueno S, Saeki Y, Soga F, Hirano M, Yanagihara T . Decrease of the D3 dopamine receptor mRNA expression in lymphocytes from patients with Parkinson's disease. Neurology. 1996; 46(3):791-5. DOI: 10.1212/wnl.46.3.791. View

13.

Marcellino D, Ferre S, Casado V, Cortes A, Le Foll B, Mazzola C . Identification of dopamine D1-D3 receptor heteromers. Indications for a role of synergistic D1-D3 receptor interactions in the striatum. J Biol Chem. 2008; 283(38):26016-25. PMC: 2533781. DOI: 10.1074/jbc.M710349200. View

14.

Torvinen M, Marcellino D, Canals M, Agnati L, Lluis C, Franco R . Adenosine A2A receptor and dopamine D3 receptor interactions: evidence of functional A2A/D3 heteromeric complexes. Mol Pharmacol. 2004; 67(2):400-7. DOI: 10.1124/mol.104.003376. View

15.

Straub R, Grum F, Strauch U, Capellino S, Bataille F, Bleich A . Anti-inflammatory role of sympathetic nerves in chronic intestinal inflammation. Gut. 2008; 57(7):911-21. DOI: 10.1136/gut.2007.125401. View

16.

Xue L, Li X, Chen Q, He J, Dong Y, Wang J . Associations between D3R expression in synovial mast cells and disease activity and oxidant status in patients with rheumatoid arthritis. Clin Rheumatol. 2018; 37(10):2621-2632. DOI: 10.1007/s10067-018-4168-1. View

17.

Gaskill P, Calderon T, Coley J, Berman J . Drug induced increases in CNS dopamine alter monocyte, macrophage and T cell functions: implications for HAND. J Neuroimmune Pharmacol. 2013; 8(3):621-42. PMC: 4303241. DOI: 10.1007/s11481-013-9443-y. View

18.

Salvi R, Steigleder T, Schlachetzki J, Waldmann E, Schwab S, Winner B . Distinct Effects of Chronic Dopaminergic Stimulation on Hippocampal Neurogenesis and Striatal Doublecortin Expression in Adult Mice. Front Neurosci. 2016; 10:77. PMC: 4786557. DOI: 10.3389/fnins.2016.00077. View

19.

Shao W, Zhang S, Tang M, Zhang X, Zhou Z, Yin Y . Suppression of neuroinflammation by astrocytic dopamine D2 receptors via αB-crystallin. Nature. 2012; 494(7435):90-4. DOI: 10.1038/nature11748. View

20.

Beggiato S, Antonelli T, Tomasini M, Borelli A, Agnati L, Tanganelli S . Adenosine A2A-D2 receptor-receptor interactions in putative heteromers in the regulation of the striato-pallidal gaba pathway: possible relevance for parkinson's disease and its treatment. Curr Protein Pept Sci. 2014; 15(7):673-80. DOI: 10.2174/1389203715666140901103205. View