Dopamine receptor DR2 expression in B cells is negatively correlated with disease activity in rheumatoid arthritis patients

Wei, Lei; Zhang, C.; Chen, Huiyao; Zhang, Z.J.; Ji, Zhihong; Yue, Tao; Dai, Xiaojuan; Zhu, Qi; Ma, Liang; He, Dongyi; Jiang, Libo

doi:10.1016/j.imbio.2014.10.016

Cited by 20 publications

(15 citation statements)

References 39 publications

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“…D5R levels in B lymphocytes from RA and osteoarthritis patients are lower than in healthy volunteers, whereas those of D2R and D3R are higher [ 133 ]; Nakano and colleagues have suggested that DA that is released by DCs activates the IL-6-Th17 axis, aggravating synovial inflammation in RA [ 246 ]. Thus, clinical protocols have been developed in which clinical researchers should use D2R agonists, such as bromocriptine and cabergoline, to lower prolactin synthesis and secretion by infiltrating synovial fibroblasts and lymphocytes in patients with RA—the improvement in RA activity might be attributed to a significant decrease in the secretion of prolactin by immune cells [ 247 , 248 ], although these results are not conclusive.…”

Section: Clinical Implications Of the Effects On The Dopaminergic mentioning

confidence: 99%

Immunomodulatory Effects Mediated by Dopamine

Arreola

Álvarez-Herrera

Pérez‐Sánchez

et al. 2016

Journal of Immunology Research

109

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Dopamine (DA), a neurotransmitter in the central nervous system (CNS), has modulatory functions at the systemic level. The peripheral and central nervous systems have independent dopaminergic system (DAS) that share mechanisms and molecular machinery. In the past century, experimental evidence has accumulated on the proteins knowledge that is involved in the synthesis, reuptake, and transportation of DA in leukocytes and the differential expression of the D1-like (D1R and D5R) and D2-like receptors (D2R, D3R, and D4R). The expression of these components depends on the state of cellular activation and the concentration and time of exposure to DA. Receptors that are expressed in leukocytes are linked to signaling pathways that are mediated by changes in cAMP concentration, which in turn triggers changes in phenotype and cellular function. According to the leukocyte lineage, the effects of DA are associated with such processes as respiratory burst, cytokine and antibody secretion, chemotaxis, apoptosis, and cytotoxicity. In clinical conditions such as schizophrenia, Parkinson disease, Tourette syndrome, and multiple sclerosis (MS), there are evident alterations during immune responses in leukocytes, in which changes in DA receptor density have been observed. Several groups have proposed that these findings are useful in establishing clinical status and clinical markers.

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Section: Clinical Implications Of the Effects On The Dopaminergic mentioning

confidence: 99%

Immunomodulatory Effects Mediated by Dopamine

Arreola

Álvarez-Herrera

Pérez‐Sánchez

et al. 2016

Journal of Immunology Research

109

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“…These changes in CIA or RA diseases may represent a compensatory protection mechanism against further deterioration of the diseases. This explanation is supported by the finding that the level of DRD2 expression on lymphocytes in RA patients negatively correlates with the disease activity [ 51 ]. In addition, the same authors [ 51 ] found that DRD2 expression level is lower on lymphocytes in RA patients than in healthy individuals.…”

Section: Discussionmentioning

confidence: 68%

“…This explanation is supported by the finding that the level of DRD2 expression on lymphocytes in RA patients negatively correlates with the disease activity [ 51 ]. In addition, the same authors [ 51 ] found that DRD2 expression level is lower on lymphocytes in RA patients than in healthy individuals. This seems to be inconsistent with our present result showing that DRD2 expression on lymphocytes in CIA mice was increased.…”

Section: Discussionmentioning

confidence: 68%

Dopamine D2 Receptor Is Involved in Alleviation of Type II Collagen-Induced Arthritis in Mice

Liu

Deng

et al. 2015

BioMed Research International

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Human and murine lymphocytes express dopamine (DA) D2-like receptors including DRD2, DRD3, and DRD4. However, their roles in rheumatoid arthritis (RA) are less clear. Here we showed that lymphocyte DRD2 activation alleviates both imbalance of T-helper (Th)17/T-regulatory (Treg) cells and inflamed symptoms in a mouse arthritis model of RA. Collagen-induced arthritis (CIA) was prepared by intradermal injection of chicken collagen type II (CII) in tail base of DBA/1 mice or Drd2 −/− C57BL/6 mice. D2-like receptor agonist quinpirole downregulated expression of proinflammatory Th17-related cytokines interleukin- (IL-) 17 and IL-22 but further upregulated expression of anti-inflammatory Treg-related cytokines transforming growth factor- (TGF-) β and IL-10 in lymphocytes in vitro and in ankle joints in vivo in CIA mice. Quinpirole intraperitoneal administration reduced both clinical arthritis score and serum anti-CII IgG level in CIA mice. However, Drd2 −/− CIA mice manifested more severe limb inflammation and higher serum anti-CII IgG level and further upregulated IL-17 and IL-22 expression and downregulated TGF-β and IL-10 expression than wild-type CIA mice. In contrast, Drd1 −/− CIA mice did not alter limb inflammation or anti-CII IgG level compared with wild-type CIA mice. These results suggest that DRD2 activation is involved in alleviation of CIA symptoms by amelioration of Th17/Treg imbalance.

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“… 11 – 13 Anatomic studies have demonstrated the expression of dopamine in dendritic cells in the synovial tissue from patients with RA, as well as the expression of D1–D5 receptors on B cells and fibroblasts from patients with RA. 10 , 14 Interestingly, a study 14 has shown an increased expression of D2-like receptors on B cells in synovial fluids from RA patients, and administration of a D2-like receptor agonist decreased arthritic scores in mice with collagen-induced RA. 10 , 15 Moreover, both administration of D2-like receptor antagonist and genetic ablation of this receptor exacerbate arthritic scores in a collagen-induced RA mouse model and in a human RA/severe combined immunodeficiency (SCID) mouse chimera model, respectively.…”

Section: Introductionmentioning

confidence: 99%

Repeated administration of mazindol reduces spontaneous pain-related behaviors without modifying bone density and microarchitecture in a mouse model of complete Freund’s adjuvant-induced knee arthritis

et al. 2017

JPR

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BackgroundThe role of dopaminergic system in the development of rheumatoid arthritis-related pain, a major symptom in this disease, has not been explored. Therefore, the anti-nociceptive effect of mazindol, a dopamine uptake inhibitor, was evaluated in a model of complete Freund’s adjuvant (CFA)-induced arthritis. Furthermore, as studies have shown that the dopaminergic system regulates bone metabolism, the effect of mazindol on bone mass and microarchitecture was determined.MethodsAdult ICR male mice received intra-articular injections of either CFA or saline into the right knee joint every week. Spontaneous pain-like behaviors (flinching and guarding) and locomotor activity were assessed at day 26 post-first CFA, following which, a single intraperitoneally (i.p.) administered dose of mazindol was given (1, 3 and 10 mg/kg). Then, the antinociceptive effect of a repeated administration of 3 mg/kg mazindol (daily, i.p.; day 15–day 26) was evaluated. Additionally, at day 26, the participation of D1-like, D2-like or opioid receptors in the antinociceptive effect of mazindol was evaluated. The effect of mazindol on bone density and microarchitecture was evaluated by micro-computed tomography.ResultsAcute administration of mazindol decreased the spontaneous pain-like behaviors in a dose-dependent manner without reducing the knee edema. However, mazindol at 10 mg/kg significantly increased the locomotor activity; therefore, 3 mg/kg mazindol was used for further studies. Repeated administration of 3 mg/kg mazindol significantly decreased the pain-like behaviors without modifying locomotor activity. The antinociceptive effect of mazindol was blocked by administration of a D2-like receptor antagonist (haloperidol), but not by administration of D1-like receptor antagonist (SCH 23390) or an opioid receptor antagonist (naloxone). Repeated administration of mazindol did not significantly modify the density and microarchitecture of periarticular bone of the arthritic and nonarthritic knee joints.ConclusionResults suggest that mazindol via D2-like receptors has an antinociceptive role in mice with CFA-induced knee arthritis without modifying the bone health negatively.

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Dopamine receptor DR2 expression in B cells is negatively correlated with disease activity in rheumatoid arthritis patients

Cited by 20 publications

References 39 publications

Immunomodulatory Effects Mediated by Dopamine

Immunomodulatory Effects Mediated by Dopamine

Dopamine D2 Receptor Is Involved in Alleviation of Type II Collagen-Induced Arthritis in Mice

Repeated administration of mazindol reduces spontaneous pain-related behaviors without modifying bone density and microarchitecture in a mouse model of complete Freund’s adjuvant-induced knee arthritis

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Dopamine receptor DR2 expression in B cells is negatively correlated with disease activity in rheumatoid arthritis patients

Cited by 20 publications

References 39 publications

Immunomodulatory Effects Mediated by Dopamine

Immunomodulatory Effects Mediated by Dopamine

Dopamine D2 Receptor Is Involved in Alleviation of Type II Collagen-Induced Arthritis in Mice

Repeated administration of mazindol reduces spontaneous pain-related behaviors without modifying bone density and microarchitecture in a mouse model of complete Freund&rsquo;s adjuvant-induced knee arthritis

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Repeated administration of mazindol reduces spontaneous pain-related behaviors without modifying bone density and microarchitecture in a mouse model of complete Freund’s adjuvant-induced knee arthritis