Inflammation and Adaptive Immunity in Parkinson's Disease

Mosley, R. Lee; Hutter-Saunders, Jessica A L; Stone, Daniel B.; Gendelman, Howard E.

doi:10.1101/cshperspect.a009381

Cited by 219 publications

(166 citation statements)

References 186 publications

(130 reference statements)

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“…Our results are similar to those of In-Uk Song et al The epidemiological studies of Chen et al reported that chronic use of NSAIDs reduces the risk of development of sporadic PD. It has been suggested that levels of serum cytokines (IL-2, IL-4, IL-6, IL-10, TNF-a, INF-c, RANTES) are elevated in PD patients [4,17]. It has also been reported that there is Strong evidence has been found indicating that gastrointestinal inflammation occurs in PD patients, characterized by increased expression levels of pro-inflammatory cytokines and glial markers.…”

Section: Discussionmentioning

confidence: 94%

The increase of carcinoembryonic antigen (CEA), high-sensitivity C-reactive protein, and neutrophil/lymphocyte ratio in Parkinson’s disease

Bulut²,

et al. 2014

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The role of carcinoembryonic antigen (CEA) in Parkinson's disease (PD) has not been previously investigated. The aim of the present study was to evaluate the serum level of carcinoembryonic antigen, high-sensitivity C-reactive protein (hs-CRP), and Neutrophil/lymphocyte ratio (NLR) among patients with Parkinson's disease and to examine the relationship between these inflammatory markers. The cross-sectional design includes 51 patients with Parkinson's disease and 50 age- and sex-matched healthy controls. We investigated the differences in hs-CRP, CEA, and NLR levels between these two groups. CEA was significantly higher in PD patients relative to the control group (mean 2.40 ± 1.51 vs. 1.72 ± 0.87 (ng/mL), respectively; p = 0.015). Mean NLR was significantly higher in PD patients relative to the control group (mean 3.1 ± 1.3 vs. 2.1 ± 0.32, respectively; p < 0.001). Serum level of hs-CRP was higher in PD patients than in control group (mean 1.04 ± 0.62 and 0.54 ± 0.31, respectively; p < 0.01). Correlation analysis revealed significant correlation between hs-CRP, CEA, and Neutrophil/lymphocyte ratio (p < 0.05). This study demonstrates for the first time the association between CEA, hs-CRP, NLR, and PD. We found CEA, hs-CRP, and NLR levels to be significantly higher in the PD patients than in the normal controls.

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Section: Discussionmentioning

confidence: 94%

The increase of carcinoembryonic antigen (CEA), high-sensitivity C-reactive protein, and neutrophil/lymphocyte ratio in Parkinson’s disease

Bulut²,

et al. 2014

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“…Neuroinflammation in PD includes activation of microglia, increased secretion of cytokines and PGs, activation complement, and circulating NK cells (66). In particular, the levels of IFN-g are higher in the serum of PD patients compared with healthy donors, and freshly purified circulating NK cells from PD patients were reported to spontaneously release greater amount of IFN-g compared with healthy volunteers (67,68). The pathologic homing of NK cells to the central nervous system might help to explain the higher amount of inflammatory cytokines observed in FIGURE 5.…”

Section: Discussionmentioning

confidence: 99%

Dopamine Inhibits the Effector Functions of Activated NK Cells via the Upregulation of the D5 Receptor

Mikulak

Bozzo

Roberto

et al. 2014

The Journal of Immunology

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Several lines of evidence indicate that dopamine (DA) plays a key role in the cross-talk between the nervous and immune systems. In this study, we disclose a novel immune-regulatory role for DA: inhibition of effector functions of activated NK lymphocytes via the selective upregulation of the D5 dopaminergic receptor in response to prolonged cell stimulation with rIL-2. Indeed, engagement of this D1-like inhibitory receptor following binding with DA suppresses NK cell proliferation and synthesis of IFN-γ. The inhibition of IFN-γ production occurs through blocking the repressor activity of the p50/c-REL dimer of the NF-κB complex. Indeed, the stimulation of the D5 receptor on rIL-2–activated NK cells inhibits the binding of p50 to the microRNA 29a promoter, thus inducing a de novo synthesis of this miRNA. In turn, the increased levels of microRNA 29a were inversely correlated with the ability of NK cells to produce IFN-γ. Taken together, our findings demonstrated that DA switches off activated NK cells, thus representing a checkpoint exerted by the nervous system to control the reactivity of these innate immune effectors in response to activation stimuli and to avoid the establishment of chronic and pathologic inflammatory processes.

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“…70 Conversely, microglia activated by overexpression or aberrant expression of a-synuclein secretes inflammatory cytokines and reactivates oxygen species that contribute to neurodegeneration. 71 Although most PD cases are sporadic, approximately 5 to 10% are inherited. At least 16 gene loci (PARK1-16) have been implicated in PD, but the heritability is not fully understood.…”

Section: Animal Models Of Parkinson's Diseasementioning

confidence: 99%