Neuro-protective effects of bee venom by suppression of neuroinflammatory responses in a mouse model of Parkinson’s disease: Role of regulatory T cells

Chung, Eun‐Sung; Kim, Himchan; Lee, Gihyun; Park, Soo‐Jin; Kim, Hyunseong; Bae, Hyunsu

doi:10.1016/j.bbi.2012.08.013

Cited by 67 publications

(61 citation statements)

References 44 publications

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“…Our previous report showed that BV has therapeutic effects on the MPTP-induced mouse model of PD via modulating the neuroinflammatory response and increasing the proportion of functional Tregs (23). In this study, we showed that bvPLA 2 has neuroprotective effects by suppressing microglial activation and reducing the infiltrating CD4 + T cells in the MPTPinduced mouse model of PD.…”

Section: Discussionsupporting

confidence: 49%

“…Recently, modulation of Tregs has been proposed as a potential therapeutic approach for neuroinflammation-mediated disorders, including PD (19,21,22). We previously observed that BV has a therapeutic effect on MPTP-induced mouse models by increasing the proportion of CD4 + CD25 + Tregs (23). Tregs may increase in the periphery following the conversion of naive T cells into Tregs through Foxp3 gene expression in response to a variety of stimuli, such as TGF-b, rapamycin, and retinoic acid (24)(25)(26).…”

Section: Foxp3-expressing Cd4mentioning

confidence: 99%

“…Our previous report showed that Tregs are involved in the therapeutic effect of BVon the MPTP-induced neurotoxicity, which has been verified via Ab-mediated Treg depletion (23). To ascertain whether Tregs were involved in the DA neuronal protection by bvPLA 2 , the mice received a PC61 anti-CD25 mAb to deplete Tregs or normal anti-rat IgG1 for an isotype control for 3 d before MPTP injection.…”

Section: Bvpla 2 Is An Effective Component Of Bv That Increases the Tmentioning

confidence: 99%

“…injections of MPTP-HCl (20 mg/kg free base in saline; Sigma-Aldrich) at 2-h intervals, as previously described (23). Twelve hours after the last MPTP injection, the MPTP-injected mice received a single i.p.…”

Section: Mptp Injectionmentioning

confidence: 99%

“…+ microglia/macrophages, and CD4 + T cells in the substantia nigra (SN) was performed using the optical fractionator method on an Olympus CAST (computer-assisted stereological toolbox system) system, version 2.1.4 (Olympus, Ballerup, Denmark), as previously described (23). The sections used for counting covered the entire SN from the rostral tip of the pars compacta to the caudal end of the pars reticulate (anteroposterior, 22.06 to 24.16 mm from bregma).…”

Section: Stereological Cell Countingmentioning

confidence: 99%

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Bee Venom Phospholipase A2, a Novel Foxp3+ Regulatory T Cell Inducer, Protects Dopaminergic Neurons by Modulating Neuroinflammatory Responses in a Mouse Model of Parkinson’s Disease

Chung

Lee

et al. 2015

The Journal of Immunology

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Foxp3-expressing CD4+ regulatory T cells (Tregs) are vital for maintaining immune tolerance in animal models of various immune diseases. In the present study, we demonstrated that bee venom phospholipase A2 (bvPLA2) is the major BV compound capable of inducing Treg expansion and promotes the survival of dopaminergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. We associated this neuroprotective effect of bvPLA2 with microglial deactivation and reduction of CD4+ T cell infiltration. Interestingly, bvPLA2 had no effect on mice depleted of Tregs by injecting anti-CD25 Ab. This finding indicated that Treg-mediated modulation of peripheral immune tolerance is strongly involved in the neuroprotective effects of bvPLA2. Furthermore, our results showed that bvPLA2 directly bound to CD206 on dendritic cells and consequently promoted the secretion of PGE2, which resulted in Treg differentiation via PGE2 (EP2) receptor signaling in Foxp3−CD4+ T cells. These observations suggest that bvPLA2-CD206-PGE2-EP2 signaling promotes immune tolerance through Treg differentiation and contributes to the prevention of various neurodegenerative diseases, including Parkinson’s disease.

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Section: Discussionsupporting

confidence: 49%

Section: Foxp3-expressing Cd4mentioning

confidence: 99%

Section: Bvpla 2 Is An Effective Component Of Bv That Increases the Tmentioning

confidence: 99%

Section: Mptp Injectionmentioning

confidence: 99%

Section: Stereological Cell Countingmentioning

confidence: 99%

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Bee Venom Phospholipase A2, a Novel Foxp3+ Regulatory T Cell Inducer, Protects Dopaminergic Neurons by Modulating Neuroinflammatory Responses in a Mouse Model of Parkinson’s Disease

Chung

Lee

et al. 2015

The Journal of Immunology

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Medicinal Benefits of Bee Venom

Sekar¹,

Lum²,

Bonam³

et al. 2023

Honey

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Calcitriol restrains microglial M1 polarization and alleviates dopaminergic degeneration in hemiparkinsonian mice by boosting regulatory T‐cell expansion

Xie,

Chen,

Chen

et al. 2024

Brain and Behavior

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ObjectiveVitamin D deficiency is a risk factor for Parkinson's disease (PD) and vitamin D supplementation robustly alleviates neurodegeneration in PD models. However, the mechanisms underlying this effect require further clarification. Current evidence suggests that harnessing regulatory T cells (Treg) may mitigate neuronal degeneration. In this study, we investigated the therapeutic effects of vitamin D receptor activation by calcitriol on PD, specifically focusing on its role in Treg.MethodsHemiparkinsonian mice model was established through the injection of 6‐OHDA into the striatum. Mice were pretreated with calcitriol before 6‐OHDA injection. The motor performance, dopaminergic neuronal survival, contents of dopamine, and dopamine metabolites were evaluated. The pro‐inflammatory cytokines levels, T‐cell infiltration, mRNA expression of indicated microglial M1/M2 phenotypic markers, and microglial marker in the midbrain were detected. Populations of Treg in the splenic tissues were assessed using a flow cytometry assay. PC61 monoclonal antibody was applied to deplete Treg in vivo.ResultsWe show that calcitriol supplementation notably improved motor performance and reduced dopaminergic degeneration in the 6‐OHDA‐induced PD model. Mechanistically, calcitriol promoted anti‐inflammatory/neuroprotective Treg and inhibited pro‐inflammatory/neurodestructive effector T‐cell generation in this model. This process significantly inhibited T‐cell infiltration in the midbrain, restrained microglial activation, microglial M1 polarization, and decreased pro‐inflammatory cytokines release. This more favorable inflammatory microenvironment rescued dopaminergic degeneration. To further verify that the anti‐inflammatory effects of calcitriol are associated with Treg expansion, we applied an antibody‐mediated Treg depletion assay. As predicted, the anti‐inflammatory effects of calcitriol in the PD model were diminished following Treg depletion.ConclusionThese findings suggest that calcitriol's anti‐inflammatory and neuroprotective effects in PD are associated with its potential to boost Treg expansion.

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Neuro-protective effects of bee venom by suppression of neuroinflammatory responses in a mouse model of Parkinson’s disease: Role of regulatory T cells

Cited by 67 publications

References 44 publications

Bee Venom Phospholipase A2, a Novel Foxp3+ Regulatory T Cell Inducer, Protects Dopaminergic Neurons by Modulating Neuroinflammatory Responses in a Mouse Model of Parkinson’s Disease

Bee Venom Phospholipase A2, a Novel Foxp3+ Regulatory T Cell Inducer, Protects Dopaminergic Neurons by Modulating Neuroinflammatory Responses in a Mouse Model of Parkinson’s Disease

Medicinal Benefits of Bee Venom

Calcitriol restrains microglial M1 polarization and alleviates dopaminergic degeneration in hemiparkinsonian mice by boosting regulatory T‐cell expansion

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