Effect of PrP105‑132 on the secretion of interleukin‑6 and interleukin‑8 from microglial cells inï¿½vitro

Yang, Yun-Tian; Jin, Songqing

doi:10.3892/etm.2017.5498

Cited by 2 publications

(1 citation statement)

References 23 publications

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“…Previous studies demonstrated the effect of treatment of toxic PrP peptide in inducing microglia activation and cytokine release (135). Garcao and colleagues showed that treatment of microglia led to increased IL-6 secretion, responsible for increased neuronal death (136,137). Interestingly, none of the antibody treatment following DMT were able to affect the production and increase of TNF-a.…”

Section: Discussionmentioning

confidence: 99%

Cross-Linking Cellular Prion Protein Induces Neuronal Type 2-Like Hypersensitivity

et al. 2021

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BackgroundPrevious reports identified proteins associated with ‘apoptosis’ following cross-linking PrPC with motif-specific anti-PrP antibodies in vivo and in vitro. The molecular mechanisms underlying this IgG-mediated neurotoxicity and the role of the activated proteins in the apoptotic pathways leading to neuronal death has not been properly defined. Previous reports implicated a number of proteins, including apolipoprotein E, cytoplasmic phospholipase A2, prostaglandin and calpain with anti-PrP antibody-mediated ‘apoptosis’, however, these proteins are also known to play an important role in allergy. In this study, we investigated whether cross-linking PrPC with anti-PrP antibodies stimulates a neuronal allergenic response.MethodsInitially, we predicted the allergenicity of the epitope sequences associated with ‘neurotoxic’ anti-PrP antibodies using allergenicity prediction servers. We then investigated whether anti-PrP antibody treatment of mouse primary neurons (MPN), neuroblastoma cells (N2a) and microglia (N11) cell lines lead to a neuronal allergenic response.ResultsIn-Silico studies showed that both tail- and globular-epitopes were allergenic. Specifically, binding regions that contain epitopes for previously reported ‘neurotoxic’ antibodies such as ICSM18 (146-159), ICSM35 (91-110), POM 1 (138-147) and POM 3 (95-100) lead to activation of allergenic related proteins. Following direct application of anti-PrPC antibodies on N2a cells, we identified 4 neuronal allergenic-related proteins when compared with untreated cells. Furthermore, we identified 8 neuronal allergenic-related proteins following treatment of N11 cells with anti-PrPC antibodies prior to co-culture with N2a cells when compared with untreated cells. Antibody treatment of MPN or MPN co-cultured with antibody-treated N11 led to identifying 10 and 7 allergenic-related proteins when compared with untreated cells. However, comparison with 3F4 antibody treatment revealed 5 and 4 allergenic-related proteins respectively. Of importance, we showed that the allergenic effects triggered by the anti-PrP antibodies were more potent when antibody-treated microglia were co-cultured with the neuroblastoma cell line. Finally, co-culture of N2a or MPN with N11-treated with anti-PrP antibodies resulted in significant accumulation of NO and IL6 but not TNF-α in the cell culture media supernatant.ConclusionsThis study showed for the first time that anti-PrP antibody binding to PrPC triggers a neuronal hypersensitivity response and highlights the important role of microglia in triggering an IgG-mediated neuronal hypersensitivity response. Moreover, this study provides an important impetus for including allergenic assessment of therapeutic antibodies for neurodegenerative disorders to derive safe and targeted biotherapeutics.

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Section: Discussionmentioning

confidence: 99%

Cross-Linking Cellular Prion Protein Induces Neuronal Type 2-Like Hypersensitivity

et al. 2021

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Extracellular Vesicles, Stem Cells and the Role of miRNAs in Neurodegeneration

Belkozhayev

Al-Yozbaki

George

et al. 2022

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There are different modalities of intercellular communication governed by cellular homeostasis. In this review, we will explore one of these forms of communication called extracellular vesicles (EVs). These vesicles are released by all cells in the body and are heterogeneous in nature. The primary function of EVs is to share information through their cargo consisting of proteins, lipids and nucleic acids (mRNA, miRNA, dsDNA etc.) with other cells, which have a direct consequence on their microenvironment. We will focus on the role of EVs of mesenchymal stem cells (MSCs) in the nervous system and how these participate in intercellular communication to maintain physiological function and provide neuroprotection. However, deregulation of this same communication system could play a role in several neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, multiple sclerosis, prion disease and Huntington’s disease. The release of EVs from a cell provides crucial information to what is happening inside the cell and thus could be used in diagnostics and therapy. We will discuss and explore new avenues for the clinical applications of using engineered MSC-EVs and their potential therapeutic benefit in treating neurodegenerative diseases.

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Effect of PrP105‑132 on the secretion of interleukin‑6 and interleukin‑8 from microglial cells inï¿½vitro

Cited by 2 publications

References 23 publications

Cross-Linking Cellular Prion Protein Induces Neuronal Type 2-Like Hypersensitivity

Cross-Linking Cellular Prion Protein Induces Neuronal Type 2-Like Hypersensitivity

Extracellular Vesicles, Stem Cells and the Role of miRNAs in Neurodegeneration

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