scholarly journals Acanthamoeba culbertsoni Elicits Soluble Factors That Exert Anti-Microglial Cell Activity

2010 ◽  
Vol 78 (9) ◽  
pp. 4001-4011 ◽  
Author(s):  
Jenica L. Harrison ◽  
Gabriela A. Ferreira ◽  
Erinn S. Raborn ◽  
Audrey D. Lafrenaye ◽  
Francine Marciano-Cabral ◽  
...  
Keyword(s):  
Microglial Cell ◽  
Cell Activity ◽  
Opportunistic Pathogen ◽  
Neonatal Rat ◽  
Cell Contact ◽  
Soluble Factors ◽  
Microglial Cell Line ◽  
The Central Nervous System ◽  
Acanthamoeba Culbertsoni ◽  
Induced Apoptosis

ABSTRACT Acanthamoeba culbertsoni is an opportunistic pathogen that causes granulomatous amoebic encephalitis (GAE), a chronic and often fatal disease of the central nervous system (CNS). A hallmark of GAE is the formation of granulomas around the amoebae. These cellular aggregates consist of microglia, macrophages, lymphocytes, and neutrophils, which produce a myriad of proinflammatory soluble factors. In the present study, it is demonstrated that A. culbertsoni secretes serine peptidases that degrade chemokines and cytokines produced by a mouse microglial cell line (BV-2 cells). Furthermore, soluble factors present in cocultures of A. culbertsoni and BV-2 cells, as well as in cocultures of A. culbertsoni and primary neonatal rat cerebral cortex microglia, induced apoptosis of these macrophage-like cells. Collectively, the results indicate that A. culbertsoni can apply a multiplicity of cell contact-independent modes to target macrophage-like cells that exert antiamoeba activities in the CNS.

Characterization of a novel brain-derived microglial cell line isolated from neonatal rat brain

Glia ◽  
2001 ◽  
Vol 35 (1) ◽  
pp. 53-62 ◽  
Author(s):  
Poonlarp Cheepsunthorn ◽  
Lesley Radov ◽  
Sharon Menzies ◽  
John Reid ◽  
James R. Connor
Keyword(s):  
Rat Brain ◽  
Cell Line ◽  
Microglial Cell ◽  
Neonatal Rat ◽  
Microglial Cell Line ◽  
Neonatal Rat Brain

Design, synthesis, and anti-neuroinflammatory activity of amidecontaining dithiolethiones

2020 ◽  
Vol 16 ◽  
Author(s):  
Karrington Craig ◽  
Paula Avila ◽  
Dennis A. Brown
Keyword(s):  
Cell Line ◽  
Microglial Cell ◽  
Neuronal Cell ◽  
Activity Data ◽  
Design Synthesis ◽  
Inflammatory Damage ◽  
Immune Mediated ◽  
Microglial Cell Line ◽  
The Central Nervous System ◽  
Anti Oxidant

Background: Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system characterized by demyelination of neurons and neurodegeneration. Current MS therapies ameliorate inflammatory damage but are unable to address the degenerative aspects of the disease. Objective: In this report, we evaluate the ability of amide-based dithiolethiones (DTTs) to suppress neuroinflammation in microglia and increase anti-oxidant capacity neuron-like cells. Methods: A series of amide-containing DTTs were designed, synthesized, and assayed for ability to suppress proneuroinflammatory cytokines IL-12p40 and IL-23p19 induced by LPS in the BV2 microglial cell line. Lead analog 2c was identified and further characterized. Results: Structure-activity data revealed tolerance towards a variety of amides. Morpholine analog 2c dose-dependently reduced various other inflammatory cytokines and mediators, including TNF, IL-6, IL-1β, NOS2, and COX2. Additionally, 2c elevated cellular levels of glutathione in SH-SH5Y neuronal cell line. Furthermore, mechanistic studies showed 2c increased the expression of anti-inflammatory Nrf2 and HMOX proteins. Conclusion: The combination of anti-neuroinflammatory and anti-oxidant activities of amide-based DTTs suggest they are promising agents for the treatment of both demyelination and neurodegeneration in MS.

Evaluating nitric oxide produced by rat inflamed microglial cell Lline, CHME-5, under the effect of IMOD

2021 ◽  
Vol 67 (2) ◽  
pp. 138-141
Author(s):  
Yu-Wei Wu ◽  
Jun-Yao Long ◽  
Xiao-Gang Liu ◽  
Hong-Qiao Fan
Keyword(s):  
Nitric Oxide ◽  
Microglial Cell ◽  
Elisa Test ◽  
Microglial Cell Line ◽  
Cell Groups ◽  
The Central Nervous System ◽  
Immunomodulatory Drug ◽  
Anti Inflammatory ◽  
High Concentrations ◽  
Myelin Degradation

Nitric oxide (NO), as a free radical, is produced by inflamed microglia cells and is one of the destructive factors of the immune system and a factor in myelin degradation. Therefore, inhibition of microglia activity is a chief strategy in reducing neurotoxic damage to the central nervous system. In this study, an herbal Immunomodulatory Drug (IMOD) was used to evaluate the effects of this drug in controlling the amount of nitric oxide. Nitric oxide induction was performed by bacterial lipopolysaccharide (LPS) in rat inflamed microglial cell line, CHME-5. ELISA test was used to measure the produced nitric oxide at 24, 48, and 72 hours. The results showed that the high concentrations of IMOD (1.2, and 4% V/V) had anti-inflammatory effects on microglial cells and were able to reduce the amount of nitric oxide in these cells but the effective dose of IMOD was in the range of 1.2% V/V. Therefore, the safest dose and the best time for the effect of IMOD on inflammatory cell groups are 1.2% V/V and 72h, respectively. Hence, with further studies, IMOD can be considered as an herbal anti-inflammatory drug that is effective in controlling neurodegenerative diseases.

scholarly journals TREM2 alters the phagocytic, apoptotic and inflammatory response to Aβ42 in HMC3 cells

2020 ◽  
Author(s):  
Rumana Akhter ◽  
Yvonne Shao ◽  
Shane Formica ◽  
Maria Khrestian ◽  
Lynn M. Bekris
Keyword(s):  
Inflammatory Response ◽  
Microglial Cell ◽  
Amyloid Β ◽  
Inflammatory Factors ◽  
Genetic Studies ◽  
Microglial Cell Line ◽  
Induced Apoptosis ◽  
The Brain ◽  
Phagocytic Response ◽  
Pro Inflammatory Cytokines

AbstractAlzheimer’s disease (AD) is characterized by the accumulation in the brain of extracellular amyloid β (Aβ) plaques as well as intraneuronal inclusions (neurofibrillary tangles) consisting of total tau and phosphorylated tau. Also present are dystrophic neurites, loss of synapses, neuronal death, and gliosis. AD genetic studies have highlighted the importance of inflammation in this disease by identifying several risk associated immune response genes, including TREM2. TREM2 has been strongly implicated in basic microglia function including, phagocytosis, apoptosis, and the inflammatory response to Aβ in mouse brain and primary cells. These studies show that microglia are key players in the response to Aβ and in the accumulation of AD pathology. However, details are still missing about which apoptotic or inflammatory factors rely on TREM2 in their response to Aβ, especially in human cell lines. Given these previous findings our hypothesis is that TREM2 influences the response to Aβ toxicity by enhancing phagocytosis and inhibiting both the BCL-2 family of apoptotic proteins and pro-inflammatory cytokines. Aβ42 treatment of the human microglial cell line, HMC3 cells, was performed and TREM2 was overexpressed or silenced and the phagocytosis, apoptosis and inflammatory response were evaluated. Results indicate that a robust phagocytic response to Aβ after 24 hours requires TREM2 in HMC3 cells. Also, TREM2 inhibits Aβ induced apoptosis by activating the Mcl-1/Bim complex. TREM2 is involved in activation of IP-10, MIP-1a, and IL-8, while it inhibits FGF-2, VEGF and GRO. Taken together, TREM2 plays a role in enhancing the microglial functional response to Aβ toxicity in HMC3 cells. This novel information suggests that therapeutic strategies that seek to activate TREM2 may not only enhance phagocytosis, but it may also inhibit beneficial inflammatory factors, emphasizing the need to define TREM2-related inflammatory activity in not only mouse models of AD, but also in human AD.

scholarly journals Neuronutraceuticals Modulate Lipopolysaccharide- or Amyloid-β 1-42 Peptide-Induced Transglutaminase 2 Overexpression as a Marker of Neuroinflammation in Mouse Microglial Cells

2021 ◽  
Vol 11 (12) ◽  
pp. 5718
Author(s):  
Nicola Gaetano Gatta ◽  
Andrea Parente ◽  
Francesca Guida ◽  
Sabatino Maione ◽  
Vittorio Gentile
Keyword(s):  
Microglial Cell ◽  
Amyloid Β ◽  
Transglutaminase 2 ◽  
Microglial Cells ◽  
Tissue Type ◽  
Microglial Cell Line ◽  
Bv2 Cells ◽  
Important Marker

Background: Tissue type 2 transglutaminase (TG2, E.C. 2.3.2,13) is reported to be involved in the phagocytosis of apoptotic cells in mouse microglial BV2 cells and peripheral macrophages. In this study, by using lipopolysaccharide (LPS)- or amyloid-β 1-42 (Aβ 1-42) peptide-stimulated microglial cell line BV2 and mouse primary microglial cells, we examined the effects of different neuronutraceutical compounds, such as curcumin (Cu) and N-Palmitoylethanolamine (PEA), known for their anti-inflammatory activity, on TG2 and several inflammatory or neuroprotective biomarker expressions. Methods: Mouse BV2 cells were treated with LPS or Aβ1-42 in the presence of curcumin or PEA, in order to evaluate the expression of TG2 and other inflammatory or neuroprotective markers using Real Time-PCR and Western blot analyses. Results: Curcumin and PEA were capable of reducing TG2 expression in mouse microglial cells during co-treatment with LPS or Aβ 1-42. Conclusions: The results show the role of TG2 as an important marker of neuroinflammation and suggest a possible use of curcumin and PEA in order to reduce LPS- or Aβ1-42-induced TG2 overexpression in mouse microglial cells.

Abstract 028: CCN1 Enables Fas Ligand-Induced Apoptosis by Elevating Fas Expression in Primary Cardiomyocytes or by Increasing Cytoplasmic Smac in Cardiomyoblast H9c2 Cells

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Bor-Chyuan Su ◽  
Fan-E Mo
Keyword(s):  
Cell Surface ◽  
Fas Ligand ◽  
Ischemia Reperfusion ◽  
Surface Display ◽  
Critical Role ◽  
Mitogen Activated Protein Kinase ◽  
Neonatal Rat ◽  
Ros Generation ◽  
H9c2 Cells ◽  
Induced Apoptosis

Fas/Fas ligand (FasL) is implicated in cardiac ischemia/reperfusion injury. However, cardiomyocytes in culture are resistant to FasL-induced apoptosis, suggesting that additional factor(s) are required for FasL-induced apoptosis. Matricellular protein CCN1 has been demonstrated to promote cytotoxicity of FasL in human skin fibroblasts. CCN1 is induced in a variety of cardiac pathologies. We assessed the hypothesis that CCN1 may be involved in the regulation of FasL-induced apoptosis in cardiomyocytes. We found that either FasL or CCN1 did not induce cell death in neonatal rat ventricular cardiomyocytes (NRVM). Interestingly, the combination of FasL+CCN1 generated 2-fold induction of apoptosis (vs. control p<0.001). An integrin-α 6 β 1 -binding defective mutant CCN1, CCN1-DM failed to exert synergy with FasL to induce apoptosis, indicating a critical role of α 6 β 1 . The engagement between CCN1 and α 6 β 1 instigated the elevation of cellular reactive oxygen species (ROS), the activation of mitogen activated protein kinase p38, and followed by the induction of cell surface display of Fas, thereby sensitizing NRVM to FasL-induced apoptosis. Pretreatment of the p38 inhibitor SB202190 abolished the CCN1-induced cell-surface Fas expression and the apoptosis induced by FasL+CCN1. In addition, we tested the interaction between CCN1 and FasL on the cardiomyoblast H9c2 cells. We found that FasL or CCN1 alone did not cause apoptosis in H9c2, and required the combination of FasL+CCN1 to induced apoptosis (vs. control p<0.001) in H9c2 cells, reminiscent of the observation in NRVM. Mechanistically, CCN1 acted through binding to integrin α 6 β 1 , ROS generation, and p38 activation, however, did not increase the expression of cell surface Fas for its synergy with FasL in H9c2 cells. Instead, CCN1 induced Bax translocation to mitochondria, which in turn led to the release of Smac from mitochondria to cytosol. The cytosolic Smac functions to neutralize XIAP. Smac is critical for CCN1 action, because the knockdown of Smac blunted the apoptotic activities of CCN1. In conclusion, CCN1 may play a detrimental role in a stressed heart to both the differentiated cardiomyocytes and the proliferative cardioblasts through distinct signaling mechanisms.

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