scholarly journals An analysis of the mechanism of aging: endogenous viral stimulus and the deleterious effect of chronic inflammation

2019 ◽  
Author(s):  
Chingis Ochirov
Keyword(s):  
Extracellular Matrix ◽  
Immune System ◽  
Signaling Pathway ◽  
Chronic Inflammation ◽  
Innate Immune System ◽  
Mapk Pathway ◽  
Lipid Synthesis ◽  
Innate Immune ◽  
Endogenous Retroviruses ◽  
Ros Production

This article describes a putative mechanism of aging based on the interaction of endogenous viral particles with the receptors of the innate immune system leading to producing pro-inflammatory cytokines. The innate immune response induces a complex of signaling pathways leading to senescence or tumorigenesis. The fate of a cell is depended on the activity of the p53 tumor-suppressive signaling pathway. Chronic inflammation is characterized by upregulation of the NF-kB signaling. The NF-kB protein stimulates the expression of matrix metalloproteinases (MMPs) leading to remodeling of extracellular matrix. The extracellular matrix alterations induce the loss of stem cell environment and their depletion. The innate immune system also mediates the PI3K-Akt-mTOR signaling pathway that inhibits autophagy and transforms energy metabolism providing cell senescence, high level of blood glucose, high lipid synthesis and mitochondrial alterations. The STAT3-HIF1 signaling pathway suppresses oxidative phosphorylation increasing ROS production and promoting the MAPK pathway leading to excessive cell proliferation. The increased ROS production causes the global DNA and histone demethylation contributing to retrotransposon reactivation whose activity leads to genome instability. However, the activity of retrotransposons may be partly explained by their role in adaptation. Among retrotransposons, endogenous retroviruses may be considered as an intrinsic stimulus for the innate immune system and are also able to avoid the adaptive immune system. Therefore, I consider endogenous retroviruses as promising targets in anti-aging therapies

scholarly journals An analysis of the mechanism of aging: endogenous viral stimulus and the deleterious effect of chronic inflammation

2019 ◽  
Author(s):  
Chingis Ochirov
Keyword(s):  
Extracellular Matrix ◽  
Immune System ◽  
Signaling Pathway ◽  
Chronic Inflammation ◽  
Innate Immune System ◽  
Mapk Pathway ◽  
Lipid Synthesis ◽  
Innate Immune ◽  
Endogenous Retroviruses ◽  
Ros Production

This article describes a putative mechanism of aging based on the interaction of endogenous viral particles with the receptors of the innate immune system leading to producing pro-inflammatory cytokines. The innate immune response induces a complex of signaling pathways leading to senescence or tumorigenesis. The fate of a cell is depended on the activity of the p53 tumor-suppressive signaling pathway. Chronic inflammation is characterized by upregulation of the NF-kB signaling. The NF-kB protein stimulates the expression of matrix metalloproteinases (MMPs) leading to remodeling of extracellular matrix. The extracellular matrix alterations induce the loss of stem cell environment and their depletion. The innate immune system also mediates the PI3K-Akt-mTOR signaling pathway that inhibits autophagy and transforms energy metabolism providing cell senescence, high level of blood glucose, high lipid synthesis and mitochondrial alterations. The STAT3-HIF1 signaling pathway suppresses oxidative phosphorylation increasing ROS production and promoting the MAPK pathway leading to excessive cell proliferation. The increased ROS production causes the global DNA and histone demethylation contributing to retrotransposon reactivation whose activity leads to genome instability. However, the activity of retrotransposons may be partly explained by their role in adaptation. Among retrotransposons, endogenous retroviruses may be considered as an intrinsic stimulus for the innate immune system and are also able to avoid the adaptive immune system. Therefore, I consider endogenous retroviruses as promising targets in anti-aging therapies

scholarly journals An analysis of the mechanism of aging: endogenous viral stimulus and the deleterious effect of chronic inflammation

2018 ◽  
Author(s):  
Chingis Ochirov
Keyword(s):  
Extracellular Matrix ◽  
Immune System ◽  
Signaling Pathway ◽  
Chronic Inflammation ◽  
Innate Immune System ◽  
Mapk Pathway ◽  
Lipid Synthesis ◽  
Innate Immune ◽  
Endogenous Retroviruses ◽  
Ros Production

This article describes a putative mechanism of aging based on the interaction of endogenous viral particles with the receptors of the innate immune system leading to producing pro-inflammatory cytokines. The innate immune response induces a complex of signaling pathways leading to senescence or tumorigenesis. The fate of a cell is depended on the activity of the p53 tumor-suppressive signaling pathway. Chronic inflammation is characterized by upregulation of the NF-kB signaling. The NF-kB protein stimulates the expression of matrix metalloproteinases (MMPs) leading to remodeling of extracellular matrix. The extracellular matrix alterations induce the loss of stem cell environment and their depletion. The innate immune system also mediates the PI3K-Akt-mTOR signaling pathway that inhibits autophagy and transforms energy metabolism providing cell senescence, high level of blood glucose, high lipid synthesis and mitochondrial alterations. The STAT3-HIF1 signaling pathway suppresses oxidative phosphorylation increasing ROS production and promoting the MAPK pathway leading to excessive cell proliferation. The increased ROS production causes the global DNA and histone demethylation contributing to retrotransposon reactivation whose activity leads to genome instability. However, the activity of retrotransposons may be partly explained by their role in adaptation. Among retrotransposons, endogenous retroviruses may be considered as an intrinsic stimulus for the innate immune system and are also able to avoid the adaptive immune system. Therefore, I consider endogenous retroviruses as promising targets in anti-aging therapies

scholarly journals An analysis of the mechanism of aging: endogenous viral stimulus and the deleterious effect of chronic inflammation

2019 ◽  
Author(s):  
Chingis Ochirov
Keyword(s):  
Extracellular Matrix ◽  
Immune System ◽  
Signaling Pathway ◽  
Chronic Inflammation ◽  
Innate Immune System ◽  
Mapk Pathway ◽  
Lipid Synthesis ◽  
Innate Immune ◽  
Endogenous Retroviruses ◽  
Ros Production

This article describes a putative mechanism of aging based on the interaction of endogenous viral particles with the receptors of the innate immune system leading to producing pro-inflammatory cytokines. The innate immune response induces a complex of signaling pathways leading to senescence or tumorigenesis. The fate of a cell is depended on the activity of the p53 tumor-suppressive signaling pathway. Chronic inflammation is characterized by upregulation of the NF-kB signaling. The NF-kB protein stimulates the expression of matrix metalloproteinases (MMPs) leading to remodeling of extracellular matrix. The extracellular matrix alterations induce the loss of stem cell environment and their depletion. The innate immune system also mediates the PI3K-Akt-mTOR signaling pathway that inhibits autophagy and transforms energy metabolism providing cell senescence, high level of blood glucose, high lipid synthesis and mitochondrial alterations. The STAT3-HIF1 signaling pathway suppresses oxidative phosphorylation increasing ROS production and promoting the MAPK pathway leading to excessive cell proliferation. The increased ROS production causes the global DNA and histone demethylation contributing to retrotransposon reactivation whose activity leads to genome instability. However, the activity of retrotransposons may be partly explained by their role in adaptation. Among retrotransposons, endogenous retroviruses may be considered as an intrinsic stimulus for the innate immune system and are also able to avoid the adaptive immune system. Therefore, I consider endogenous retroviruses as promising targets in anti-aging therapies

scholarly journals THU0010 GENES ASSOCIATED WITH NUCLEOTIDE OLIGOMERIZATION DOMAIN-LIKE RECEPTOR SIGNALING PATHWAY ARE UPREGULATED IN CUTANEOUS LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 217.3-217
Author(s):  
I. Calderon ◽  
R. Mina
Keyword(s):  
Immune System ◽  
Signaling Pathway ◽  
Lupus Erythematosus ◽  
Innate Immune System ◽  
Cutaneous Lupus Erythematosus ◽  
Skin Lesions ◽  
Innate Immune ◽  
Normal Controls ◽  
Cutaneous Lupus ◽  
Skin Samples

Background:Cutaneous Lupus Erythematosus (CLE) is a disfiguring autoimmune skin disorder with several subtypes: discoid lupus, subacute cutaneous lupus, and acute cutaneous lupus. CLE is associated with defects in the adaptive immune system, and, at times, systemic involvement. The innate immune system is likely involved as seen in the presence of interface dermatitis, which is observed in viral exanthems, and improvement of CLE using inhibitors to membrane-bound Pattern Recognition Receptors.Objectives:Compare the expression of genes associated with the innate immune system in active CLE skin lesions of different subtypes compared to normal skin controls.Methods:Five datasets selected from the Gene Expression Omnibus (GEO) were analyzed using GEO2R to compare the gene expressions between different subtypes of CLE. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, Gene Card, and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis were used to identify the interaction and function of specific genes.Results:There were a total of 147 CLE skin samples and 52 normal controls. Genes associated with the Nucleotide-Binding Oligomerization Domain-Like Receptor (NLR) signaling pathway were upregulated in CLE skin samples (adjusted p-value < 0.001). Five genes associated with the NLR signaling pathway, STAT1, OAS1, OAS2, OAS3, and AIM2, were found to be upregulated in skin samples of CLE patients in all datasets, regardless of type, compared to normal controls in all datasets. These five genes are associated with transcription activation, regulation of viral infection, and interferon response.Conclusion:Genes associated with the NLR signaling pathway are upregulated in the skin lesions of CLE patients compared to normal controls, supporting the role of the innate immune system in CLE. Further validation studies using experimental methods are needed.References:[1]Enhanced inflammasome activity in systemic lupus erythematosus is mediated via type I interferon upregulation of interferon regulatory factor 1. Liu J, et al. Arth Rheum. 2017; 69(9): 1840-1849.Disclosure of Interests:None declared

scholarly journals Role of pattern recognition receptors of the neurovascular unit in inflamm-aging

2017 ◽  
Vol 313 (5) ◽  
pp. H1000-H1012 ◽  
Author(s):  
Imola Wilhelm ◽  
Ádám Nyúl-Tóth ◽  
Mihály Kozma ◽  
Attila E. Farkas ◽  
István A. Krizbai
Keyword(s):  
Pattern Recognition ◽  
Immune System ◽  
Chronic Inflammation ◽  
Blood Brain Barrier ◽  
Innate Immune System ◽  
Neurovascular Unit ◽  
Innate Immune ◽  
Brain Barrier ◽  
Pyrin Domain ◽  
The Brain

Aging is associated with chronic inflammation partly mediated by increased levels of damage-associated molecular patterns, which activate pattern recognition receptors (PRRs) of the innate immune system. Furthermore, many aging-related disorders are associated with inflammation. PRRs, such as Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain-like receptors (NLRs), are expressed not only in cells of the innate immune system but also in other cells, including cells of the neurovascular unit and cerebral vasculature forming the blood-brain barrier. In this review, we summarize our present knowledge about the relationship between activation of PRRs expressed by cells of the neurovascular unit-blood-brain barrier, chronic inflammation, and aging-related pathologies of the brain. The most important damage-associated molecular pattern-sensing PRRs in the brain are TLR2, TLR4, and NLR family pyrin domain-containing protein-1 and pyrin domain-containing protein-3, which are activated during physiological and pathological aging in microglia, neurons, astrocytes, and possibly endothelial cells and pericytes.

scholarly journals Bcr and Abr Cooperate in Negatively Regulating Acute Inflammatory Responses

2009 ◽  
Vol 29 (21) ◽  
pp. 5742-5750 ◽  
Author(s):  
Jess M. Cunnick ◽  
Sabine Schmidhuber ◽  
Gang Chen ◽  
Min Yu ◽  
Sun-Ju Yi ◽  
...  
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Inflammatory Responses ◽  
Small Gtpase ◽  
Innate Immune ◽  
Ros Production ◽  
Activated Neutrophils ◽  
Inflammatory Processes ◽  
Null Mutant Mice

ABSTRACT Bcr and Abr are GTPase-activating proteins for the small GTPase Rac. Both proteins are expressed in cells of the innate immune system, including neutrophils and macrophages. The function of Bcr has been linked to the negative regulation of neutrophil reactive oxygen species (ROS) production, but the function of Abr in the innate immune system was unknown. Here, we report that mice lacking both proteins are severely affected in two models of experimental endotoxemia, including exposure to Escherichia coli lipopolysaccharide and polymicrobial sepsis, with extensive microvascular leakage, resulting in severe pulmonary edema and hemorrhage. Additionally, in vivo-activated neutrophils of abr and bcr null mutant mice produced excessive tissue-damaging myeloperoxidase (MPO), elastase, and ROS. Moreover, the secretion of the tissue metalloproteinase MMP9 by monocytes and ROS by elicited macrophages was abnormally high. In comparison, ROS production from bone marrow monocytes was not significantly different from that of controls, and the exocytosis of neutrophil secondary and tertiary granule products, including lactoferrin, was normal. These data show that Abr and Bcr normally curb very specific functions of mature tissue innate immune cells, and that each protein has distinct as well as partly overlapping functions in the downregulation of inflammatory processes.

scholarly journals A one-protein signaling pathway in the innate immune system

2016 ◽  
Vol 1 (2) ◽  
pp. eaah6184-eaah6184
Author(s):  
Megan H. Orzalli ◽  
Jonathan C. Kagan
Keyword(s):  
Immune System ◽  
Signaling Pathway ◽  
Innate Immune System ◽  
Innate Immune ◽  
Protein Signaling

Acute-phase responses and adipocytokines

2013 ◽  
Author(s):  
Elena Neumann ◽  
Klaus Frommer ◽  
Ulf Müller-Ladner
Keyword(s):  
Adipose Tissue ◽  
Immune System ◽  
Chronic Inflammation ◽  
Acute Phase ◽  
Innate Immune System ◽  
Current Knowledge ◽  
Cell Types ◽  
Innate Immune ◽  
Bioactive Substances ◽  
Different Cell Types

Adipokines, also called adipocytokines, are highly bioactive substances mainly expressed by adipose tissue. In addition to adipocytes, different cell types resident in various tissues produce adipokines under pathophysiological conditions. Adipokines include a growing number of pluripotent molecules such as adiponectin, resistin, leptin, and visfatin. Since distinct effects of adipokines on inflammation have been described, their influence on the (innate) immune system has been investigated in rheumatology, gastroenterology, and endocrinology. This review gives an overview on the current knowledge about the influence which adipokines have on the immune system and chronic inflammation in rheumatic diseases.

L-Threonine upregulates β-defensins expression by activating NF-κB signaling pathway and suppressing SIRT1 expression in porcine intestinal epithelial cells

2021 ◽  
Author(s):  
Chenxi Wang ◽  
Yang Yang ◽  
Nan Gao ◽  
Jing Lan ◽  
Xiujing Dou ◽  
...  
Keyword(s):  
Immune System ◽  
Epithelial Cells ◽  
Antimicrobial Peptide ◽  
Signaling Pathway ◽  
Innate Immune System ◽  
Intestinal Epithelial Cells ◽  
Innate Immune ◽  
Pivotal Role ◽  
Intestinal Epithelial ◽  
New Strategy

The use of antimicrobial peptide (AMP), found in all forms of life and playing a pivotal role in the innate immune system, has been developed as a new strategy for...

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