Dopamine D1-like receptor antagonist, SCH23390, exhibits a preventive effect on diabetes mellitus that occurs naturally in NOD mice

Hashimoto, Kumiko; Inoue, Tsutomu; Higashi, Taishi; Takei, Shinichiro; Awata, Takuya; Katayama, Shigehiro; Takagi, Ryukichi; Okada, Hirokazu; Matsushita, Sho

doi:10.1016/j.bbrc.2009.04.034

Cited by 24 publications

(26 citation statements)

References 22 publications

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“…D1-like-R antagonist suppressed their increase, suggesting that D1-like-R antagonist would suppress Th17 differentiation of the existing cells. Moreover, an in vivo study showed D1-like-R antagonist attenuates Th17-mediated immune disease such as EAE (14), autoimmune diabetes in NOD mice (17), and crescent formation of nephrotoxic serum nephritis (18). These findings suggested that dopamine played an important role in the development of Th17-mediated immune disease and that D1-like-R or D2-like-R could be an important therapeutic target for controlling Th17-mediated neutrophilic airway inflammation.…”

Section: Discussionmentioning

confidence: 96%

“…From weeks 26 to 0, some mice received one of the D1-like-R antagonists SCH23390 (0.3 mg/kg; Sigma-Aldrich), SKF83566 (0.3 mg/kg; Tocris Bioscience, Bristol, U.K.), or LE300 (0.3 mg/kg; Tocris Bioscience) in PBS (50 ml) or PBS alone orally three times a week as previously reported (14,17,18). The mice were analyzed on day 1.…”

Section: Induction Of Airway Inflammation and Administration Of D1-limentioning

confidence: 99%

“…Immunohistochemistry was performed as previously reported (17). Briefly, the tissue was deparaffinized and rehydrated with decreasing concentrations of ethyl alcohol.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…D1 and D5 form the D1-like group, which leads to an increase in intracellular cAMP formation, whereas D2, D3, and D4 form the D2-like group, which leads to a decrease in intracellular cAMP formation (16). We also reported that antagonizing dopamine D1-like receptor (D1-like-R) could attenuate Th17-mediated (or Th17-involved) immune disease such as experimental autoimmune encephalomyelitis (EAE) (14), autoimmune diabetes (17), and nephrotoxic serum nephritis (18). However, whether antagonism of D1-like-R can suppress Th17-type response in the airway has yet to be studied.…”

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confidence: 99%

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Dopamine D1-Like Receptor Antagonist Attenuates Th17-Mediated Immune Response and Ovalbumin Antigen-Induced Neutrophilic Airway Inflammation

Nakagome

Imamura

Okada

et al. 2011

The Journal of Immunology

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Allergic airway inflammation is generally considered a Th2-type immune response. Recent studies, however, demonstrated that Th17-type immune responses also play important roles in this process, especially in the pathogenesis of neutrophilic airway inflammation, a hallmark of severe asthma. We previously reported that dendritic cells release dopamine to naive CD4+ T cells in Ag-specific cell–cell interaction, in turn inducing Th17 differentiation through dopamine D1-like receptor (D1-like-R). D1-like-R antagonist attenuates Th17-mediated diseases such as experimental autoimmune encephalomyelitis and autoimmune diabetes. However, the effect of antagonizing D1-like-R on Th17-mediated airway inflammation has yet to be studied. In this study, we examined whether D1-like-R antagonist suppresses OVA-induced neutrophilic airway inflammation in OVA TCR-transgenic DO11.10 mice and then elucidated the mechanism of action. DO11.10 mice were nebulized with OVA or PBS, and some mice received D1-like-R antagonist orally before OVA nebulization. D1-like-R antagonist significantly suppressed OVA-induced neutrophilic airway inflammation in DO11.10 mice. It also inhibited the production of IL-17 and infiltration of Th17 cells in the lung. Further, D1-like-R antagonist suppressed the production of IL-23 by lung CD11c+ APCs. In contrast, D1-like-R antagonist did not increase Foxp3+ regulatory T cells in the lung. D1-like-R antagonist neither suppressed nonspecific LPS-induced neutrophilic airway inflammation nor OVA-induced eosinophilic airway inflammation. These results indicate that D1-like-R antagonist could suppress Th17-mediated neutrophilic airway inflammation, raising the possibility that antagonizing D1-like-R serves as a promising new strategy for treating neutrophil-dominant severe asthma.

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Section: Discussionmentioning

confidence: 96%

Section: Induction Of Airway Inflammation and Administration Of D1-limentioning

confidence: 99%

“…Immunohistochemistry was performed as previously reported (17). Briefly, the tissue was deparaffinized and rehydrated with decreasing concentrations of ethyl alcohol.…”

Section: Immunohistochemistrymentioning

confidence: 99%

mentioning

confidence: 99%

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Dopamine D1-Like Receptor Antagonist Attenuates Th17-Mediated Immune Response and Ovalbumin Antigen-Induced Neutrophilic Airway Inflammation

Nakagome

Imamura

Okada

et al. 2011

The Journal of Immunology

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“…In other words, application of a D1-like receptor antagonist can be expected to control autoimmune disorders such as RA via two mechanisms: inhibition of IL-6-Th17 bias and increase in Treg activity. Actually, D1-like receptor antagonists exhibited preventive and therapeutic effects on model mice of autoimmune diseases such as EAE in mice, diabetes mellitus that occurs naturally in NOD mice, and crescent formation in nephrotoxic serum nephritis mice (19,66,67).…”

Section: Discussionmentioning

confidence: 99%

Dopamine Induces IL-6–Dependent IL-17 Production via D1-Like Receptor on CD4 Naive T Cells and D1-Like Receptor Antagonist SCH-23390 Inhibits Cartilage Destruction in a Human Rheumatoid Arthritis/SCID Mouse Chimera Model

Nakano

Yamaoka

Hanami

et al. 2011

The Journal of Immunology

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111

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A major neurotransmitter dopamine transmits signals via five different seven-transmembrane G protein-coupled receptors termed D1–D5. Several studies have shown that dopamine not only mediates interactions into the nervous system, but can contribute to the modulation of immunity via receptors expressed on immune cells. We have previously shown an autocrine/paracrine release of dopamine by dendritic cells (DCs) during Ag presentation to naive CD4+ T cells and found efficacious results of a D1-like receptor antagonist SCH-23390 in the experimental autoimmune encephalomyelitis mouse model of multiple sclerosis and in the NOD mouse model of type I diabetes, with inhibition of Th17 response. This study aimed to assess the role of dopaminergic signaling in Th17-mediated immune responses and in the pathogenesis of rheumatoid arthritis (RA). In human naive CD4+ T cells, dopamine increased IL-6–dependent IL-17 production via D1-like receptors, in response to anti-CD3 plus anti-CD28 mAb. Furthermore, dopamine was localized with DCs in the synovial tissue of RA patients and significantly increased in RA synovial fluid. In the RA synovial/SCID mouse chimera model, although a selective D2-like receptor antagonist haloperidol significantly induced accumulation of IL-6+ and IL-17+ T cells with exacerbated cartilage destruction, SCH-23390 strongly suppressed these responses. Taken together, these findings indicate that dopamine released by DCs induces IL-6–Th17 axis and causes aggravation of synovial inflammation of RA, which is the first time, to our knowledge, that actual evidence has shown the pathological relevance of dopaminergic signaling with RA.

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Dopamine in the Immune System: Dopamine Receptors in Immune Cells, Potent Effects, Endogenous Production and Involvement in Immune and Neuropsychiatric Diseases

Levite

2012

Nerve-Driven Immunity

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Dopamine D1-like receptor antagonist, SCH23390, exhibits a preventive effect on diabetes mellitus that occurs naturally in NOD mice

Cited by 24 publications

References 22 publications

Dopamine D1-Like Receptor Antagonist Attenuates Th17-Mediated Immune Response and Ovalbumin Antigen-Induced Neutrophilic Airway Inflammation

Dopamine D1-Like Receptor Antagonist Attenuates Th17-Mediated Immune Response and Ovalbumin Antigen-Induced Neutrophilic Airway Inflammation

Dopamine Induces IL-6–Dependent IL-17 Production via D1-Like Receptor on CD4 Naive T Cells and D1-Like Receptor Antagonist SCH-23390 Inhibits Cartilage Destruction in a Human Rheumatoid Arthritis/SCID Mouse Chimera Model

Dopamine in the Immune System: Dopamine Receptors in Immune Cells, Potent Effects, Endogenous Production and Involvement in Immune and Neuropsychiatric Diseases

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