A novel approach to study markers of dopamine signaling in peripheral immune cells

Gopinath, Adithya; Doty, Andria; Mackie, Phillip; Hashimi, Basil; Francis, Madison; Saadatpour, Leila; Saha, Kaustuv; Shaw, Gerry; Ramirez‐Zamora, Adolfo; Okun, Michael S.; Streit, Wolfgang J.; Khoshbouei, Habibeh

doi:10.1016/j.jim.2019.112686

Cited by 21 publications

(39 citation statements)

References 24 publications

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“…Two million monocytes isolated from whole blood of healthy donors were treated for 4 hours with tissue plasminogen activator (TPA, 100ng/mL, positive control for increased monocyte TH expression 7 ), TNFδ (17ng/mL) 61 and compared with monocytes treated with vehicle (Figure 6A). Monocytes were assayed for TH expression by two complementary methods: flow cytometry 51 (Figure 6B-F) and ELISA (Figure 6G-H). We should note that because a prolonged TNFδ exposure can induce cell toxicity 82–86 , we tested multiple treatment durations.…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…PBMCs express TH 43, 51 . As previously published 51 , whole blood was collected in K2EDTA vacutainer blood collection tubes (BD, 366643) and held at room temperature for up to 2 hours prior to PBMC isolation. Briefly, blood from healthy volunteers and PD patients was overlaid in Leucosep tubes (Table 2) for PBMC isolation, centrifuged for 20 minutes at 400g with brakes turned off and acceleration set to minimum.…”

Section: Methodsmentioning

confidence: 99%

“…Suspended cells from each treatment group were aspirated and placed in a 15mL conical tube, with any remaining adherent cells detached by incubation with 700uL Accumax solution for 3 minutes (Innovative Cell Technologies, AM105) and added to suspended cells. After pelleting cells by centrifugation (3 minutes x 100g, room temperature), cells were assayed by either flow cytometry 38 or lysed for ELISA as stated above ("Preparation of cell lysates").…”

Section: Xpro1595 and Il6mentioning

confidence: 99%

“…Given the plethora of biological systems expressing TH, there is an unmet need for a sensitive and reliable assay to quantify TH levels which with broad biological implications in basic science, preclinical and clinical research. To date, measurement of TH levels in midbrain neurons has been accomplished by immunohistochemistry, and Western blot [49][50][51][52] , while TH levels in peripheral immune cells has been assayed by flow cytometry 38 . Although reliable, these methods share a common shortcoming in that they are semi-quantitative at best, and at worst only indicate the presence or absence of TH.…”

Section: Bio-elisa Successfully and Reproducibly Detects Recombinant And Native Thmentioning

confidence: 99%

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TNFα increases Tyrosine Hydroxylase expression in human monocytes

Gopinath

Badova

Francisa

et al. 2021

Preprint

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Most, if not all, peripheral immune cells in humans and animals express tyrosine hydroxylase (TH), the rate limiting enzyme in catecholamine synthesis. Since TH is typically studied in the context of brain catecholamine signaling, little is known about changes in TH production and function in peripheral immune cells. This knowledge gap is due, in part, to the lack of an adequately sensitive assay to measure TH in immune cells expressing lower TH levels compared to other TH expressing cells. Here, we report the development of a highly sensitive and reproducible Bio-ELISA to quantify picogram levels of TH in multiple model systems. We have applied this assay to monocytes isolated from blood of persons with Parkinson's disease (PD) and to age-matched, healthy controls. Our study unexpectedly revealed that PD patients' monocytes express significantly higher levels of TH protein in peripheral monocytes relative to healthy controls. Tumor necrosis factor (TNF), a pro- inflammatory cytokine, has also been shown to be increased in the brains and peripheral circulation in human PD, as well as in animal models of PD. Therefore, we investigated a possible connection between higher levels of TH protein and the known increase in circulating TNF in PD. Monocytes isolated from healthy donors were treated with TNF or with TNF in the presence of an inhibitor. Tissue plasminogen activator (TPA) was used as a positive control. We observed that TNF stimulation increased both the number of TH+ monocytes and the quantity of TH per monocyte, without increasing the total numbers of monocytes. These results revealed that TNF could potentially modify monocytic TH production and serve a regulatory role in peripheral immune function. The development and application of a highly sensitive assay to quantify TH in both human and animal cells will provide a novel tool for further investigating possible PD immune regulatory pathways between brain and periphery.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Xpro1595 and Il6mentioning

confidence: 99%

Section: Bio-elisa Successfully and Reproducibly Detects Recombinant And Native Thmentioning

confidence: 99%

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TNFα increases Tyrosine Hydroxylase expression in human monocytes

Gopinath

Badova

Francisa

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

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Dopaminergic regulation of inflammation and immunity in Parkinson's disease: friend or foe?

Furgiuele,

Pereira,

Martini

et al. 2023

Clin & Trans Imm

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Parkinson's disease (PD) is a neurodegenerative disease affecting 7–10 million people worldwide. Currently, there is no treatment available to prevent or delay PD progression, partially due to the limited understanding of the pathological events which lead to the death of dopaminergic neurons in the substantia nigra in the brain, which is known to be the cause of PD symptoms. The current available treatments aim at compensating dopamine (DA) deficiency in the brain using its precursor levodopa, dopaminergic agonists and some indirect dopaminergic agents. The immune system is emerging as a critical player in PD. Therefore, immune‐based approaches have recently been proposed to be used as potential antiparkinsonian agents. It has been well‐known that dopaminergic pathways play a significant role in regulating immune responses in the brain. Although dopaminergic agents are the primary antiparkinsonian treatments, their immune regulatory effect has yet to be fully understood. The present review summarises the current available evidence of the immune regulatory effects of DA and its mimics and discusses dopaminergic agents as antiparkinsonian drugs. Based on the current understanding of their involvement in the regulation of neuroinflammation in PD, we propose that targeting immune pathways involved in PD pathology could offer a better treatment outcome for PD patients.

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Assessment of the relationship between the dopaminergic pathway and severe acute respiratory syndrome coronavirus 2 infection, with related neuropathological features, and potential therapeutic approaches in COVID‐19 infection

Rasmi,

Shokati,

Hatamkhani

et al. 2024

Reviews in Medical Virology

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Dopamine is a known catecholamine neurotransmitter involved in several physiological processes, including motor control, motivation, reward, cognition, and immune function. Dopamine receptors are widely distributed throughout the nervous system and in immune cells. Several viruses, including human immunodeficiency virus and Japanese encephalitis virus, can use dopaminergic receptors to replicate in the nervous system and are involved in viral neuropathogenesis. In addition, studies suggest that dopaminergic receptors may play a role in the progression and pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. When SARS‐CoV‐2 binds to angiotensin‐converting enzyme 2 receptors on the surface of neuronal cells, the spike protein of the virus can bind to dopaminergic receptors on neighbouring cells to accelerate its life cycle and exacerbate neurological symptoms. In addition, recent research has shown that dopamine is an important regulator of the immune‐neuroendocrine system. Most immune cells express dopamine receptors and other dopamine‐related proteins, indicating the importance of dopaminergic immune regulation. The increase in dopamine concentration during SARS‐CoV2 infection may reduce immunity (innate and adaptive) that promotes viral spread, which could lead to neuronal damage. In addition, dopaminergic signalling in the nervous system may be affected by SARS‐CoV‐2 infection. COVID ‐19 can cause various neurological symptoms as it interacts with the immune system. One possible treatment strategy for COVID ‐19 patients could be the use of dopamine antagonists. To fully understand how to protect the neurological system and immune cells from the virus, we need to study the pathophysiology of the dopamine system in SARS‐CoV‐2 infection.

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A novel approach to study markers of dopamine signaling in peripheral immune cells

Cited by 21 publications

References 24 publications

TNFα increases Tyrosine Hydroxylase expression in human monocytes

TNFα increases Tyrosine Hydroxylase expression in human monocytes

Dopaminergic regulation of inflammation and immunity in Parkinson's disease: friend or foe?

Assessment of the relationship between the dopaminergic pathway and severe acute respiratory syndrome coronavirus 2 infection, with related neuropathological features, and potential therapeutic approaches in COVID‐19 infection

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