Senile plaques in the Alzheimer's disease (AD) are formed by aggregation of beta-amyloid (Abeta) peptide. Abeta peptide has been shown to activate microglia and stimulate their production of inflammatory factors, such as cytokines. In the AD brain, the continued presence of amyloid plaques may keep microglia persistently activated, leading to chronic inflammation in the CNS. It is well established that alpha-melanocyte-stimulating hormone (alpha-MSH) gives rise to anti-inflammatory and anti-pyretic effects. The biological activities of alpha-MSH are mediated by one or more of the melanocortin receptor (MCR) subtypes, i.e. MCR1 - MCR5. The aim of the present study was to determine the effect of alpha-MSH alone and on Abeta-activated microglial cells with regard to the secretion of inflammatory cytokines, such as interleukin-6 (IL-6), and to determine which receptor subtype mediates the effects of alpha-MSH. The human microglial cell line, CHME3, was incubated for 24 h with freshly dissolved Abeta(1-40), interferon-gamma (IFN-gamma) and/or alpha-MSH. Freshly dissolved Abeta(1-40) (5-60 microM) resulted in a dose-dependent decrease in cell viability, along with a dose-dependent increase in IL-6 release. Neither IFN-gamma nor alpha-MSH affected the Abeta-induced secretion of IL-6, but resulted in a dose-dependent increase in basal IL-6 release. Agouti, the endogenous antagonist of MCR1 and 4, further increased the alpha-MSH-induced secretion of IL-6. RT-PCR showed the expression of MCR1, MCR3, MCR4 and MCR5 mRNA. The combined data suggest that the effect of alpha-MSH in increasing IL-6 release from the human microglial cell line is mediated by MCR3 or MCR5.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/BF03033980 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Epidemic Zika virus strains from the Asian lineage induce an attenuated fetal brain pathogenicity.
Nat Commun
December 2024
KU Leuven Department of Microbiology, Immunology and Transplantation, Virology, Antiviral Drug & Vaccine Research Group, Rega Institute for Medical Research, Leuven, Belgium.
The 2015-2016 Zika virus (ZIKV) outbreak in the Americas revealed the ability of ZIKV from the Asian lineage to cause birth defects, generically called congenital Zika syndrome (CZS). Notwithstanding the long circulation history of Asian ZIKV, no ZIKV-associated CZS cases were reported prior to the outbreaks in French Polynesia (2013) and Brazil (2015). Whether the sudden emergence of CZS resulted from an evolutionary event of Asian ZIKV has remained unclear.
View Article and Find Full Text PDFCross-disease transcriptomic analysis reveals DOK3 and PAPOLA as therapeutic targets for neuroinflammatory and tumorigenic processes.
Front Immunol
December 2024
Emergency Department, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.
Objective: Subarachnoid hemorrhage (SAH) and tumorigenesis share numerous biological complexities; nevertheless, the specific gene expression profiles and underlying mechanisms remain poorly understood. This study aims to identify differentially expressed genes (DEGs) that could serve as biomarkers for diagnosis and prognosis.
Methods: Gene expression datasets (GSE122063, GSE13353, GSE161870) were analyzed using machine learning algorithms and logistic regression to identify DEGs associated with both SAH and tumorigenesis.
Amelioration of signaling deficits underlying metabolic shortfall in TREM2 human iPSC-derived microglia.
FEBS J
December 2024
Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, UK.
The microglial triggering receptor expressed on myeloid cells 2 (TREM2) is required for diverse microglia responses in neurodegeneration, including immunometabolic plasticity, phagocytosis, and survival. We previously identified that patient iPSC-derived microglia (iPS-Mg) harboring the Alzheimer's disease (AD) TREM2 hypomorph display several functional deficits linked to metabolism. To investigate whether these deficits are associated with disruptions in metabolite signaling, we generated common variant, TREM2 and TREM2 variant human iPS-Mg.
View Article and Find Full Text PDFN-terminus α-synuclein detection reveals new and more diverse aggregate morphologies in multiple system atrophy and Parkinson's disease.
Transl Neurodegener
December 2024
Department of Anatomy and Medical Imaging, University of Auckland, 85 Park Road, Grafton, , Auckland, 1142, New Zealand.
Background: Parkinson's disease (PD) and multiple system atrophy (MSA) are classified as α-synucleinopathies and are primarily differentiated by their clinical phenotypes. Delineating these diseases based on their specific α-synuclein (α-Syn) proteoform pathologies is crucial for accurate antemortem biomarker diagnosis. Newly identified α-Syn pathologies in PD raise questions about whether MSA exhibits a similar diversity.
View Article and Find Full Text PDFHigher CSF sTREM2 attenuates APOE ε4-related risk for amyloid pathology in cognitively intact adults: The CABLE study.
J Neurochem
January 2025
Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
The triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane protein found in microglia within the brain, and its soluble form (sTREM2) has been shown to reduce amyloid deposition. Whether elevated TREM2-mediated microglial activity decreases the risk of Alzheimer's disease (AD) is unclear. The aim of this study was to assess whether high cerebrospinal fluid (CSF) levels of sTREM2 attenuate the risk of APOE ε4-associated amyloid pathology.
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!