The immunoregulatory role of dopamine: An update

Sarkar, Chandrani; Basu, Biswarup; Chakroborty, Debanjan; Dasgupta, Partha Sarthi; Basu, Sujit

doi:10.1016/j.bbi.2009.10.015

Cited by 276 publications

(224 citation statements)

References 43 publications

(97 reference statements)

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“…During the past two decades, several studies have shown the capability of several neurotransmitters to regulate the function and differentiation of immune cells, including acetyl-choline, serotonin, glutamate, and dopamine (DA) among others (11)(12)(13)(14)(15)(16)(17)(18). Regarding expression of DA receptors (DARs) in immune cells, these receptors have been found not only in cells of the innate immune response such as dendritic cells (DCs), NK cells, macrophages/monocytes and granulocytes (19)(20)(21) but also in cells of the adaptive immune response such as B cells, CD8 + T cells, and CD4 + T cells (22)(23)(24)(25)(26)(27)(28)(29)(30).…”

Section: P Arkinson's Disease (Pd) Is a Neurodegenerative Disordermentioning

confidence: 99%

Dopamine Receptor D3 Expressed on CD4+ T Cells Favors Neurodegeneration of Dopaminergic Neurons during Parkinson’s Disease

González

Contreras

Prado

et al. 2013

The Journal of Immunology

127

145

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Emerging evidence has demonstrated that CD4+ T cells infiltrate into the substantia nigra (SN) in Parkinson's disease (PD) patients and in animal models of PD. SN-infiltrated CD4+ T cells bearing inflammatory phenotypes promote microglial activation and strongly contribute to neurodegeneration of dopaminergic neurons. Importantly, altered expression of dopamine receptor D3 (D3R) in PBLs from PD patients has been correlated with disease severity. Moreover, pharmacological evidence has suggested that D3R is involved in IFN-γ production by human CD4+ T cells. In this study, we examined the role of D3R expressed on CD4+ T cells in neurodegeneration of dopaminergic neurons in the SN using a mouse model of PD. Our results show that D3R-deficient mice are strongly protected against loss of dopaminergic neurons and microglial activation during 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. Notably, D3R-deficient mice become susceptible to MPTP-induced neurodegeneration and microglial activation upon transfer of wild-type (WT) CD4+ T cells. Furthermore, RAG1 knockout mice, which are devoid of T cells and are resistant to MPTP-induced neurodegeneration, become susceptible to MPTP-induced loss of dopaminergic neurons when reconstituted with WT CD4+ T cells but not when transferred with D3R-deficient CD4+ T cells. In agreement, experiments analyzing activation and differentiation of CD4+ T cells revealed that D3R favors both T cell activation and acquisition of the Th1 inflammatory phenotype. These findings indicate that D3R expressed on CD4+ T cells plays a fundamental role in the physiopathology of MPTP-induced PD in a mouse model.

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Section: P Arkinson's Disease (Pd) Is a Neurodegenerative Disordermentioning

confidence: 99%

Dopamine Receptor D3 Expressed on CD4+ T Cells Favors Neurodegeneration of Dopaminergic Neurons during Parkinson’s Disease

González

Contreras

Prado

et al. 2013

The Journal of Immunology

127

145

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“…In addition to its conventional role in the brain, recent reports indicate that DA also controls several functions in the periphery (8,9). DA has been shown to regulate behavior, movement, and cardiovascular, renal, endocrine, gastrointestinal, and immune functions (8)(9)(10). Normal blood vessels are supplied by sympathetic nerves, and neurotransmitters released from these nerve endings regulate many critical vascular functions (8,(11)(12)(13)(14)(15).…”

mentioning

confidence: 99%

Dopamine stabilizes tumor blood vessels by up-regulating angiopoietin 1 expression in pericytes and Krüppel-like factor-2 expression in tumor endothelial cells

Chakroborty

Sarkar

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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100

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Impaired blood flow in the tumor vascular bed caused by structurally and functionally abnormal blood vessels not only hinders the delivery of chemotherapeutic agents but also aggravates tumor hypoxia, making the tumor cells further resistant to antineoplastic drugs. Therefore, normalization of tumor blood vessels may be an important approach to increase therapeutic efficacy in the treatment of cancer patients. As blood vessels are supplied by sympathetic nerves containing dopamine (DA), and DA regulates functions of normal blood vessels through its receptors present in these vessels, we investigated the effect of DA on tumor vasculature. Here we report loss of sympathetic innervation and endogenous DA in abnormal and immature tumor blood vessels in malignant colon and prostate tumor tissues. In contrast, exogenous administration of DA normalizes the morphology and improves the functions of these vessels by acting on pericytes and endothelial cells, the two major cellular components of blood vessels. DA acts through its D 2 receptors present in these cells to up-regulate directly the expression of angiopoietin 1 (Ang1) in pericytes and the expression of the zinc finger transcriptional factor, Krüppel-like factor-2 (KLF2) in tumor endothelial cells. Importantly, this vessel stabilization by DA also significantly increases the concentration of anticancer drug in tumor tissues. These results show a relationship between vascular stabilization and a neurotransmitter and indicate that DA or its D 2 receptor-specific agonists can be an option for the treatment of cancer and disorders in which normalization of blood vessels may have therapeutic benefits.I t now is well established that tumor blood vessels are structurally and functionally abnormal (1-4). In contrast to normal blood vessels, which are well organized and lined by quiescent adult endothelial cells and supporting mature pericytes, tumor vessels are highly disorganized and made up of active endothelial cells (1-6). Moreover, in these tumor vessels pericytes are lacking or immature pericytes attach loosely to the endothelial cells (1-3). This vascular immaturity in turn causes destabilization of vessel structure, impairment of endothelial barrier function, and decreased blood flow leading to increased hypoxia in tumor tissues (1-3). In addition, the impaired blood flow in abnormal tumor blood vessels not only compromises the delivery of anticancer drugs but also aggravates tumor hypoxia, making tumor cells more resistant to these agents (1-3). Thus, stabilization or normalization of tumor vessels can be an important approach to increase the therapeutic efficacy of anticancer drugs (1, 7). Dopamine (DA) is a monoamine catecholamine neurotransmitter, which acts through its D 1 and D 2 class of receptors present in the target organs (8, 9). In addition to its conventional role in the brain, recent reports indicate that DA also controls several functions in the periphery (8, 9). DA has been shown to regulate behavior, movement, and cardiovascular, renal, endocrine...

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“…mune system as well as a mediator produced and released by immune cells themselves [31]. Several studies now indicate the presence of DA D1, D2, D3, D4 and D5 receptors in normal human leukocytes.…”

Section: Fig 2 Clinical and Macroscopic Features Of Iodoacetamide-imentioning

confidence: 99%

Role of peripheral dopaminergic system in the pathogenesis of experimental colitis in rats

Prysiazhniuk¹,

Rudyk²,

Chervinska³

et al. 2017

Ukr.Biochem.J.

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dopamine (dA) is produced and released by immune cells. recent data pointed to dA as a key mediator between the nervous and immune systems.In the present study we tested the hypothesis that peripheral dopaminergic system plays a negative role in ulcerative colitis pathogenesis via the effect on activity of peripheral blood phagocytes. The study was conducted on male Wistar rats (170-200 g). The peripheral dopaminergic system was destroyed by 2,3,

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The immunoregulatory role of dopamine: An update

Cited by 276 publications

References 43 publications

Dopamine Receptor D3 Expressed on CD4+ T Cells Favors Neurodegeneration of Dopaminergic Neurons during Parkinson’s Disease

Dopamine Receptor D3 Expressed on CD4+ T Cells Favors Neurodegeneration of Dopaminergic Neurons during Parkinson’s Disease

Dopamine stabilizes tumor blood vessels by up-regulating angiopoietin 1 expression in pericytes and Krüppel-like factor-2 expression in tumor endothelial cells

Role of peripheral dopaminergic system in the pathogenesis of experimental colitis in rats

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