IL-1β, IL-2, IL-6 and TNF-α production by peripheral blood mononuclear cells from patients with Parkinson's disease

Bessler, Hanna; Djaldetti, Ruth; Salman, Hertzel; Bergman, Michael; Djaldetti, M

doi:10.1016/s0753-3322(99)80079-1

Cited by 130 publications

(83 citation statements)

References 9 publications

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“…Previous studies have investigated the production of cytokines in cultures of peripheral blood mononuclear cells (PBMCs), and isolated monocytes under stimulation with LPS and have shown contradictory results. Bessler et al [36] showed that PBMCs from PD patients produced higher levels of IL-1β and IL-6 after activation with LPS than those from controls. In contrast, Hasegawa et al [37] reported a decrease in TNF, IL-1β, and IL-6 production in LPS-activated PBMC cultures of patients with PD in comparison with cultures of healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Decreased Toll-Like Receptor 2 and Toll-Like Receptor 7/8-Induced Cytokines in Parkinson's Disease Patients

Silva

Borges

Souza

et al. 2016

Neuroimmunomodulation

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Objectives: Toll-like receptors (TLRs) are expressed in several immune cells including blood monocytes and resident macrophages, such as microglia in the central nervous system. TLRs recognize pathogen- or damage-associated molecular patterns, leading to the release of inflammatory and toxic molecules, which can contribute to neuroinflammation associated with Parkinson's disease (PD). The aim of this study was to compare the potential of peripheral blood cells from PD patients or healthy subjects to produce cytokines after exposure to TLR agonists, and to investigate TLR2 and TLR4 expression on monocyte subsets. Methods: Twenty-one patients and 21 healthy controls were recruited. Patients were evaluated according to the Unified Parkinson's Disease Rating Scale, and Hoehn and Yahr stage. Cytokines were measured in supernatants of whole blood cultures after incubation with TLR2, TLR4, or TLR7/8 agonists, by cytometric bead array. Expression of CD14, CD16, TLR2, and TLR4 was analyzed by cytometry. Results: Patient blood cells produced lower levels of cytokines in response to TLR2 and also after TLR7/8/R848 activation than controls. Percentages of CD14⁺CD16⁺ or CD14⁺CD16^- monocytes and TLR2 and TLR4 expression were similar between patients and controls. Conclusions: Blood leukocyte TLR2 and TLR7/8 responses are impaired in PD. This was neither associated with imbalance in monocyte subsets nor with TLR2/TLR4 expression on these cells. The association between a decreased TLR response in periphery and damage of brain in PD must be further investigated.

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Section: Discussionmentioning

confidence: 99%

Decreased Toll-Like Receptor 2 and Toll-Like Receptor 7/8-Induced Cytokines in Parkinson's Disease Patients

Silva

Borges

Souza

et al. 2016

Neuroimmunomodulation

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“…It is well known that inflammation plays an important role in dopaminergic neurodegeneration in humans and the animal MPTP model of PD (Mogi et al 1994, Hunot et al 1996, Bessler et al 1999, Dehmer et al 2000, Nagatsu et al 2000, Sriram et al 2002. Given the fact that exendin-4 suppressed the MPTP-induced microglial response, we investigated if the expression of microglia-derived pro-inflammatory mediators in the midbrain is suppressed by exendin-4 treatment.…”

Section: Effect Of Exendin-4 On the Production Of Microglia-derived Dmentioning

confidence: 99%

Exendin-4 protects dopaminergic neurons by inhibition of microglial activation and matrix metalloproteinase-3 expression in an animal model of Parkinson's disease

Kim

Moon²,

Park

2009

Journal of Endocrinology

231

179

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Exendin-4 is a naturally occurring more potent and stable analog of glucagon-like peptide-1 (GLP-1) that selectively binds at the GLP-1 receptor. It has been recently demonstrated that GLP-1 receptor stimulation preserves dopaminergic neurons in cellular and rodent models of Parkinson's disease (PD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes nigrostriatal dopaminergic neurotoxicity in rodents; previous studies suggest that activated microglia actively participate in the pathogenesis of PD neurodegeneration. However, the role of microglia in the neuroprotective properties of exendin-4 is still unknown. Here, we show that, in the mouse MPTP PD model, systemic administration of exendin-4 significantly attenuates the loss of substantia nigra pars compacta (SNpc) neurons and the striatal dopaminergic fibers. Exendin-4 prevents MPTP-induced microglial activation in the SNpc and striatum, and the expression of matrix metalloproteinase-3. In addition, exendin-4 also suppressed MPTP-induced expression of pro-inflammatory molecules and tumor necrosis factor a and interleukin-1b. Our data indicate that exendin-4 may act as a survival factor for dopaminergic neurons by functioning as a microgliadeactivating factor and suggest that exendin-4 may be a valuable therapeutic agent for neurodegenerative diseases such as PD.

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“…Of these, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) are increased in the SNpc and the cerebrospinal fluid of PD patients (Mogi et al 1994). Some of the found increases might be due to the chronic use of the anti-parkinsonian drug L-dopa (Bessler et al 1999). Nevertheless, TNF-α, IL-1β, and interferon-γ (IFN-γ) have been shown to be increased in PD and to colocalize with glia cells (Boka et al 1994;Hunot et al 1999).…”

Section: Microglial Activation In Parkinson's Diseasementioning

confidence: 99%

Cellular pathology of Parkinson?s disease: astrocytes, microglia and inflammation

2004

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Parkinson's disease (PD) is a frequent neurological disorder of the basal ganglia, which is characterized by the progressive loss of dopaminergic neurons mainly in the substantia nigra pars compacta (SNpc). Inflammatory processes have been shown to be associated with the pathogenesis of PD. Activated microglia, as well as to a lesser extent reactive astrocytes, are found in the area associated with cell loss, possibly contributing to the inflammatory process by the release of pro-inflammatory prostaglandins or cytokines. Further deleterious factors released by activated microglia or astrocytes are reactive oxygen species. On the other hand, they may mediate neuroprotective properties by the release of trophic factors or the uptake of glutamate. In this review, we will discuss the different aspects of activated glial cells and potential mechanisms that mediate or protect against cell loss in PD.

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IL-1β, IL-2, IL-6 and TNF-α production by peripheral blood mononuclear cells from patients with Parkinson's disease

Cited by 130 publications

References 9 publications

Decreased Toll-Like Receptor 2 and Toll-Like Receptor 7/8-Induced Cytokines in Parkinson's Disease Patients

Decreased Toll-Like Receptor 2 and Toll-Like Receptor 7/8-Induced Cytokines in Parkinson's Disease Patients

Exendin-4 protects dopaminergic neurons by inhibition of microglial activation and matrix metalloproteinase-3 expression in an animal model of Parkinson's disease

Cellular pathology of Parkinson?s disease: astrocytes, microglia and inflammation

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