scholarly journals Apolipoprotein E Suppresses the Type I Inflammatory Response In Vivo

2005 ◽  
Vol 97 (9) ◽  
pp. 922-927 ◽  
Author(s):  
Kamilah Ali ◽  
Melissa Middleton ◽  
Ellen Puré ◽  
Daniel J. Rader
Keyword(s):  
Inflammatory Response ◽  
Apolipoprotein E ◽  
Type I

scholarly journals NOD1 Participates in the Innate Immune Response Triggered by Hepatitis C Virus Polymerase

2016 ◽  
Vol 90 (13) ◽  
pp. 6022-6035 ◽  
Author(s):  
Serena Vegna ◽  
Damien Gregoire ◽  
Marie Moreau ◽  
Patrice Lassus ◽  
David Durantel ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Innate Immunity ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Inflammatory Response ◽  
Cellular Response ◽  
Pattern Recognition Receptors ◽  
Type I ◽  
Mitochondrial Antiviral Signaling

ABSTRACTHepatitis C virus (HCV) triggers innate immunity signaling in the infected cell. Replication of the viral genome is dispensable for this phenotype, and we along with others have recently shown that NS5B, the viral RNA-dependent RNA polymerase, synthesizes double-stranded RNA (dsRNA) from cellular templates, thus eliciting an inflammatory response, notably via activation of type I interferon and lymphotoxin β. Here, we investigated intracellular signal transduction pathways involved in this process. Using HepaRG cells, a model that largely recapitulates thein vivocomplexities of the innate immunity receptor signaling, we have confirmed that NS5B triggered increased expression of the canonical pattern recognition receptors (PRRs) specific for dsRNA, namely, RIG-I, MDA5, and Toll-like receptor 3 (TLR3). Unexpectedly, intracellular dsRNA also led to accumulation of NOD1, a receptor classically involved in recognition of bacterial peptidoglycans. NOD1 activation, confirmed by analysis of its downstream targets, was likely due to its interaction with dsRNA and was independent of RIG-I and mitochondrial antiviral signaling protein (MAVS/IPS-1/Cardif/VISA) signaling. It is likely to have a functional significance in the cellular response in the context of HCV infection since interference with the NOD1 pathway severely reduced the inflammatory response elicited by NS5B.IMPORTANCEIn this study, we show that NOD1, a PRR that normally senses bacterial peptidoglycans, is activated by HCV viral polymerase, probably through an interaction with dsRNA, suggesting that NOD1 acts as an RNA ligand recognition receptor. In consequence, interference with NOD1-mediated signaling significantly weakens the inflammatory response to dsRNA. These results add a new level of complexity to the understanding of the cross talk between different classes of pattern recognition receptors and may be related to certain complications of chronic hepatitis C virus infection.

scholarly journals Apolipoprotein E Isoforms Differentially Regulate Alzheimer’s Disease and Amyloid-β-Induced Inflammatory Response in vivo and in vitro

2017 ◽  
Vol 57 (4) ◽  
pp. 1265-1279 ◽  
Author(s):  
Evan Dorey ◽  
Michelle Bamji-Mirza ◽  
Dema Najem ◽  
Yan Li ◽  
Hong Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inflammatory Response ◽  
Apolipoprotein E ◽  
Amyloid Β

scholarly journals Imaging Collagen in Intact Viable Healthy and Atherosclerotic Arteries Using Fluorescently Labeled CNA35 and Two-Photon Laser Scanning Microscopy

2007 ◽  
Vol 6 (4) ◽  
pp. 7290.2007.00021 ◽  
Author(s):  
Remco T.A. Megens ◽  
Mirjam G.A. oude Egbrink ◽  
Jack P.M. Cleutjens ◽  
Marijke J.E. Kuijpers ◽  
Paul H.M. Schiffers ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Apolipoprotein E ◽  
Carotid Arteries ◽  
Ex Vivo ◽  
Atherosclerotic Plaques ◽  
Type I ◽  
Two Photon ◽  
Tunica Adventitia ◽  
Molecular Imaging Agent

We evaluated CNA35 as a collagen marker in healthy and atherosclerotic arteries of mice after both ex vivo and in vivo administration and as a molecular imaging agent for the detection of atherosclerosis. CNA35 conjugated with fluorescent Oregon Green 488 (CNA35/OG488) was administered ex vivo to mounted viable muscular (uterine), elastic (carotid), and atherosclerotic (carotid) arteries and fresh arterial rings. Two-photon microscopy was used for imaging. CNA35/OG488 labeling in healthy elastic arteries was compared with collagen type I, III, and IV antibody labeling in histologic sections. For in vivo labeling experiments, CNA35/OG488 was injected intravenously in C57BL6/J and apolipoprotein E−/− mice. Ex vivo CNA35/OG488 strongly labeled collagen in the tunica adventitia, media, and intima of muscular arteries. In healthy elastic arteries, tunica adventitia was strongly labeled, but labeling in tunica media and intima was prevented by endothelium and elastic laminae. Histology confirmed the affinity of CNA35 for type I, III, and IV collagen in arteries. Strong CNA35/OG488 labeling was found in atherosclerotic plaques. In vivo applied CNA35/OG488 minimally labeled the tunica intima of healthy carotid arteries. Atherosclerotic plaques in apolipoprotein E−/− mice exhibited large uptake. CNA35/OG488 imaging in organs revealed endothelium as a limiting barrier for in vivo uptake. CNA35/OG488 is a good molecular imaging agent for atherosclerosis.

scholarly journals Connexin-Based Therapeutics and Tissue Engineering Approaches to the Amelioration of Chronic Pancreatitis and Type I Diabetes: Construction and Characterization of a Novel Prevascularized Bioartificial Pancreas

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
J. Matthew Rhett ◽  
Hongjun Wang ◽  
Heather Bainbridge ◽  
Lili Song ◽  
Michael J. Yost
Keyword(s):  
Chronic Pancreatitis ◽  
Inflammatory Response ◽  
Cell Survival ◽  
Islet Cell ◽  
Type I Diabetes ◽  
Type I ◽  
Bioartificial Pancreas ◽  
Insulin Degrading Enzyme ◽  
Prevascularized Tissue

Total pancreatectomy and islet autotransplantation is a cutting-edge technique to treat chronic pancreatitis and postoperative diabetes. A major obstacle has been low islet cell survival due largely to the innate inflammatory response. Connexin43 (Cx43) channels play a key role in early inflammation and have proven to be viable therapeutic targets. Even if cell death due to early inflammation is avoided, insufficient vascularization is a primary obstacle to maintaining the viability of implanted cells. We have invented technologies targeting the inflammatory response and poor vascularization: a Cx43 mimetic peptide that inhibits inflammation and a novel prevascularized tissue engineered construct. We combined these technologies with isolated islets to create a prevascularized bioartificial pancreas that is resistant to the innate inflammatory response. Immunoconfocal microscopy showed that constructs containing islets express insulin and possess a vascular network similar to constructs without islets. Glucose stimulated islet-containing constructs displayed reduced insulin secretion compared to islets alone. However, labeling for insulin post-glucose stimulation revealed that the constructs expressed abundant levels of insulin. This discrepancy was found to be due to the expression of insulin degrading enzyme. These results suggest that the prevascularized bioartificial pancreas is potentially a tool for improving long-term islet cell survivalin vivo.

scholarly journals Regulation of IFN-Is by MEF2D Promotes Inflammatory Homeostasis in Microglia

2021 ◽  
Author(s):  
Fangfang Lu ◽  
Ronglin Wang ◽  
Tiejian Nie ◽  
Fei Gao ◽  
Shaosong Yang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathway ◽  
Response Regulator ◽  
Expression Patterns ◽  
Inflammatory Factors ◽  
Type I ◽  
Immune Balance ◽  
Bv2 Cells

Abstract Background Microglia play an essential role in the host defense of central nervous system. Transcription factor MEF2D is known to participate in stress regulation of various cells and is tightly triggered in microglia in vivo and in vitro. MEF2D is shown to bind at the promoter region of several cytokine genes in immune cells, and directly regulates inflammatory response, suggesting that MEF2D may act as a key stimulus response regulator of microglia and is involved in the regulation of brain micro-homeostasis. In order to uncover the molecular mechanism of MEF2D in inflammatory system, in the present study, we investigated the global effect of MEF2D in activated microglia, and explored its potential regulatory network. Methods Experiments of recombinant lentivirus vector of shRNA and specific MEF2D over-expression were performed in BV2 cells. Transcriptome sequencing and the global gene expression patterns were analyzed in lipopolysaccharide-stimulated shMEF2D BV2 cells. The pro- and anti-inflammatory factors were assessed by western blot, qPCR or ELISA, and microglia activity by phagocytosis and morphologic analysis. The directly binding of MEF2D to the promoter regions of IRF7 were tested by ChIP-qPCR and PCR. The ISGs were tested by qPCR. Results MEF2D was shown to actively participate in the inflammatory response of BV2 microglial cells. RNAi induced stable silence of MEF2D broke the immune balance of microglia, in two ways: (1) promoted the expression of pro-inflammatory factors, such as NLRP3, IL-1β, iNOS; and (2) markedly inhibited the type-I interferon signaling pathway by directly modulating the transcription of IRF7. On the contrary, overexpression of MEF2D significantly reduced the expression of NLRP3 and iNOS under LPS stimulation, and alleviated the level of immune stress in microglia. Conclusions These findings demonstrate that MEF2D plays an important role in the regulation of inflammatory homeostasis partly through transcriptional regulation of the IFN-Is response signaling pathway.

Inhibitory effects of epimedium herb water extract on the inflammatory response in vitro and in vivo

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
YC Oh ◽  
YH Jeong ◽  
WK Cho ◽  
SJ Lee ◽  
JY Ma
Keyword(s):  
Inflammatory Response ◽  
Water Extract ◽  
Inhibitory Effects

Peculiarities of the course of type I allergic reactions in patients with blood diseases

2020 ◽  
pp. 40-50
Author(s):  
A. Nikitina
Keyword(s):  
Search Engines ◽  
Anaphylactic Shock ◽  
Type I ◽  
Allergic Reactions ◽  
Common Cause ◽  
Blood Diseases ◽  
Treatment Regimens ◽  
Modern Methods

Analysis of literature data presented in search engines — Elibrary, PubMed, Cochrane — concerning the risk of developing type I allergic reactions in patients with blood diseases is presented. It is shown that the most common cause of type I allergic reactions is drugs included in the treatment regimens of this category of patients. The article presents statistics on the increase in the number of drug allergies leading to cases of anaphylactic shock in patients with blood diseases. Modern methods for the diagnosis of type I allergic reactions in vivo and in vitro are considered.

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