Background: Alzheimer's disease (AD) is accompanied by a neuroinflammation triggering chemoattractant signals towards peripheral blood mononuclear cells (PBMCs), which in turn could reduce amyloid plaques after transmigration through the blood brain barrier (BBB). But the chemotactic environment remains unclear.
Objective: To analyze five chemokines known to be involved in AD in three different cellular models to better understand the cellular and molecular interactions in the BBB.
Method: Chemokines (CCL-2, 4 and 5, CXCL10 and CX3CL1) were measured in isolated cells, a BBB model without PBMCs (H4 and hCMEC/D3 cells, a neuroglioma and human endothelial cells, respectively) and in a complete BBB model with PBMCs from AD patients at a moderate stage. In one set of experiments, H4 cells were treated with Aβ42.
Results: CCL2 and CCL5 significantly increased in hCMEC/D3 and H4 cells in the complete BBB model. In turn, the rate of CCL2 increased in PBMCs whereas for CCL5, it decreased. CXCL10 increased in all cellular actors in the complete BBB model, compared to isolated cells. For CCL4, PBMCs induced a robust increase in H4 and hCMEC/D3. In turn, the level of CCL4 decreased in PBMCs. Furthermore, PBMCs triggered a significant increase in CX3CL1 in hCMEC/D3. Surprisingly, no effect of Aβ42 was observed in the complete BBB model.
Conclusion: These findings highlight the interest of a BBB model in order to explore chemokine production. For the first time, results showed that PBMCs from patients with AD can control the production of CCL4 and CXCL10 in a human BBB model.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2174/1567205014666170417110337 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Scalable Manufacturing Method for Model Protein-Loaded PLGA Nanoparticles: Biocompatibility, Trafficking and Release Properties.
Pharmaceutics
January 2025
MyBiotech GmbH, Industriestraße 1B, 66802 Überherrn, Germany.
: Drug delivery systems (DDSs) offer efficient treatment solutions to challenging diseases such as central nervous system (CNS) diseases by bypassing biological barriers such as the blood-brain barrier (BBB). Among DDSs, polymeric nanoparticles (NPs), particularly poly(lactic-co-glycolic acid) (PLGA) NPs, hold an outstanding position due to their biocompatible and biodegradable qualities. Despite their potential, the translation of PLGA NPs from laboratory-scale production to clinical applications remains a significant challenge.
View Article and Find Full Text PDFPolymeric Polylactic Acid-Glycolic Acid-Based Nanoparticles Deliver Nintedanib Across the Blood-Brain Barrier to Inhibit Glioblastoma Growth.
Int J Mol Sci
January 2025
The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China.
The aim of this study was to investigate the inhibitory effect of nintedanib (BIBF) on glioblastoma (GBM) cells and its mechanism of action and to optimize a drug delivery strategy to overcome the limitations posed by the blood-brain barrier (BBB). We analyzed the inhibition of GBM cell lines following BIBF treatment and explored its effect on the autophagy pathway. The cytotoxicity of BIBF was assessed using the CCK-8 assay, and further techniques such as transmission electron microscopy, Western blotting (WB), and flow cytometry were employed to demonstrate that BIBF could block the autophagic pathway by inhibiting the fusion of autophagosomes and lysosomes, ultimately limiting the proliferation of GBM cells.
View Article and Find Full Text PDFMagnetoelectric Extracellular Vesicle Latency-Targeting (MELT) Nanotherapeutic for the Block-Lock-and-Kill HIV Eradication Strategy.
Biomedicines
January 2025
Herbert Wertheim College of Medicine, Cellular and Molecular Medicine, Florida International University, Miami, FL 33199, USA.
Background: Human immunodeficiency virus (HIV) establishes latent infections in cellular reservoirs, including microglia. HC69 cells, a microglial model of HIV latency, contain an HIV promoter long terminal repeat (LTR)-GFP reporter and were used for testing the efficacy of a two-step magnetoelectric nanoparticle (MENP) and extracellular vesicle (xEV) latency-targeting (MELT) nanotherapeutic. GFP expression in HC69 at rest is low (GFP), and upon exposure to LTR, transcription-activating agents (i.
View Article and Find Full Text PDF3-HKA Promotes Vascular Remodeling After Stroke by Modulating the Activation of A1/A2 Reactive Astrocytes.
Adv Sci (Weinh)
January 2025
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
Ischemic stroke is the most common cerebrovascular disease and the leading cause of permanent disability worldwide. Recent studies have shown that stroke development and prognosis are closely related to abnormal tryptophan metabolism. Here, significant downregulation of 3-hydroxy-kynurenamine (3-HKA) in stroke patients and animal models is identified.
View Article and Find Full Text PDFIdentification of Cell Fate Determining Transcription Factors for Generating Brain Endothelial Cells.
Stem Cell Rev Rep
January 2025
Stem Cell Institute, Department of Development and Regeneration, KU Leuven, O&N IV Herestraat 49, Leuven, 3000, Belgium.
Reliable models of the blood-brain barrier (BBB), wherein brain microvascular endothelial cells (BMECs) play a key role in maintenance of barrier function, are essential tools for developing therapeutics and disease modeling. Recent studies explored generating BMEC-like cells from human pluripotent stem cells (hPSCs) by mimicking brain-microenvironment signals or genetic reprogramming. However, due to the lack of comprehensive transcriptional studies, the exact cellular identity of most of these cells remains poorly defined.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!