Assessing the Off-Target Effects of miRNA Inhibitors on Innate Immune Toll-Like Receptors

2016 ◽  
pp. 127-135 ◽  
Author(s):  
Geneviève Pépin ◽  
Jonathan Ferrand ◽  
Michael P. Gantier
Keyword(s):  
Innate Immune ◽  
Toll Like Receptors ◽  
Target Effects

scholarly journals Peptidomimetic 1-Benzyl-5-methyl-4-(n-octylamino)pyrimidin-2(1H)-one Showed Cardioprotection Effect in a Myocardial Ischemia (MI) Mouse Model

Proceedings ◽  
2019 ◽  
Vol 22 (1) ◽  
pp. 72
Author(s):  
Lena Trifonov ◽  
Vadim Nudelman ◽  
Michael Zhenin ◽  
Guy Cohen ◽  
Krzysztof Jozwiak ◽  
...  
Keyword(s):  
Immune Response ◽  
Pattern Recognition ◽  
Myocardial Ischemia ◽  
Mouse Model ◽  
Innate Immune Response ◽  
Pattern Recognition Receptor ◽  
Innate Immune ◽  
Microbial Pathogens ◽  
Toll Like Receptors ◽  
Recognition Receptor

TLR4, a member of the toll-like receptors (TLRs) family, serves as a pattern recognition receptor in the innate immune response to different microbial pathogens. [...]

scholarly journals Melanogenesis Connection with Innate Immunity and Toll-Like Receptors

2020 ◽  
Vol 21 (24) ◽  
pp. 9769
Author(s):  
Saaya Koike ◽  
Kenshi Yamasaki
Keyword(s):  
Skin Pigmentation ◽  
Innate Immune ◽  
Mitogen Activated Protein Kinase ◽  
Ultraviolet Rays ◽  
Toll Like Receptors ◽  
Pigment Formation ◽  
Living Body ◽  
Pigmentary Disorders ◽  
Wide Range ◽  
Griscelli Syndrome

The epidermis is located in the outermost layer of the living body and is the place where external stimuli such as ultraviolet rays and microorganisms first come into contact. Melanocytes and melanin play a wide range of roles such as adsorption of metals, thermoregulation, and protection from foreign enemies by camouflage. Pigmentary disorders are observed in diseases associated with immunodeficiency such as Griscelli syndrome, indicating molecular sharing between immune systems and the machineries of pigment formation. Melanocytes express functional toll-like receptors (TLRs), and innate immune stimulation via TLRs affects melanin synthesis and melanosome transport to modulate skin pigmentation. TLR2 enhances melanogenetic gene expression to augment melanogenesis. In contrast, TLR3 increases melanosome transport to transfer to keratinocytes through Rab27A, the responsible molecule of Griscelli syndrome. TLR4 and TLR9 enhance tyrosinase expression and melanogenesis through p38 MAPK (mitogen-activated protein kinase) and NFκB signaling pathway, respectively. TLR7 suppresses microphthalmia-associated transcription factor (MITF), and MITF reduction leads to melanocyte apoptosis. Accumulating knowledge of the TLRs function of melanocytes has enlightened the link between melanogenesis and innate immune system.

scholarly journals Rab8a localisation and activation by Toll-like receptors on macrophage macropinosomes

2018 ◽  
Vol 374 (1765) ◽  
pp. 20180151 ◽  
Author(s):  
Adam A. Wall ◽  
Nicholas D. Condon ◽  
Lin Luo ◽  
Jennifer L. Stow
Keyword(s):  
Immune Cell ◽  
Light Sheet ◽  
Innate Immune ◽  
Live Cells ◽  
Toll Like Receptors ◽  
Membrane Turnover ◽  
Cell Functions ◽  
Microbial Responses ◽  
Pathogen Entry ◽  
Tlr Signalling

Macropinocytosis is a prevalent and essential pathway in macrophages where it contributes to anti-microbial responses and innate immune cell functions. Cell surface ruffles give rise to phagosomes and to macropinosomes as multi-functional compartments that contribute to environmental sampling, pathogen entry, plasma membrane turnover and receptor signalling. Rapid, high resolution, lattice light sheet imaging demonstrates the dynamic nature of macrophage ruffling. Pathogen-mediated activation of surface and endosomal Toll-like receptors (TLRs) in macrophages upregulates macropinocytosis. Here, using multiple forms of imaging and microscopy, we track membrane-associated, fluorescently-tagged Rab8a expressed in live macrophages, using a variety of cell markers to demonstrate Rab8a localization and its enrichment on early macropinosomes. Production of a novel biosensor and its use for quantitative FRET analysis in live cells, pinpoints macropinosomes as the site for TLR-induced activation of Rab8a. We have previously shown that TLR signalling, cytokine outputs and macrophage programming are regulated by the GTPase Rab8a with PI3 Kγ as its effector. Finally, we highlight another effector, the phosphatase OCRL, which is located on macropinosomes and interacts with Rab8a, suggesting that Rab8a may operate on multiple levels to modulate phosphoinositides in macropinosomes. These findings extend our understanding of macropinosomes as regulatory compartments for innate immune function in macrophages. This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.

scholarly journals P0022INNATE IMMUNE RESPONSES ELICITED BY TOLL-LIKE RECEPTORS ARE POSSIBLY INVOLVED IN THE PATHOGENESIS OF NEPHROTIC SYNDROME

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Eriko Tanaka ◽  
Ichiro Hada ◽  
Naoaki Mikami ◽  
Kunimasa Yan
Keyword(s):  
Innate Immunity ◽  
Nephrotic Syndrome ◽  
Immune System ◽  
Innate Immune System ◽  
Expression Profiles ◽  
Kidney Tissue ◽  
Innate Immune ◽  
Rna Expression ◽  
Toll Like Receptors ◽  
Tissue Samples

Abstract Background and Aims Pathogenesis of idiopathic nephrotic syndrome (INS) is yet to be fully elucidated. Immunological disorders are reported to be involved in the etiology of INS. Due to the efficacy of immunosuppressant agents such as calcineurin inhibitor and rituximab in treating nephrotic syndrome, aberrant activation of the acquired immune system through T and B cells are considered to be the underlying pathogenic mechanisms of INS. Nevertheless, there is a possibility that the innate immune system plays a key role in INS pathogenesis. This study aims to investigate the involvement of innate immunity in INS pathogenesis by examining the expressions of toll-like receptors (TLRs). Method Kidney tissue samples from two INS patients were collected at two points of time: the first biopsy was performed during nephrosis and the second during remission. Total RNA was extracted from the kidney tissue samples, and RNA-sequencing was performed to investigate RNA expression profiles. The differences between RNA expression profiles of TLRs and molecules related to TLR pathways in the tissue samples collected during nephrosis and remission were analyzed. Results There was a significant decrease in RNA expression of TLR9 and TLR10 during remission compared to nephrosis: fold change in each patient was -2.12 and -2.12 for TLR9, and -2.51 and -2.09 for TLR10. RNA expression of TLR8 also decreased: fold change in each patient was -1.19 and -1.75. There were no significant changes in the RNA expression profiles of TLR1, 2, 3, 4, 5, 6, and 7. In addition, there were no differences in the RNA expression profiles of MYD88, IRAK family, and TRAF family molecules that are associated with TLR pathways. However, RNA expressions of IL6, IL1B, IL12B, and TNF, as well as the cytokines controlled by TLR8 and TLR9 pathways, which were activated during nephrosis, disappeared or decreased during remission. Conclusion The involvement of the innate immune system in the pathogenesis of nephrotic syndrome has been suggested in some reports. Based on the fact that the onset or recurrence of nephrosis is triggered by non-specific viral infection, it is highly possible that innate immunity is involved in the pathogenesis of nephrotic syndrome. TLRs play a key role in innate immunity as they elicit the innate immune system after detecting pathogens, induce inflammatory cytokine production, and trigger signaling pathways that activate lymphocytes via maturation of dendritic cells. Specifically, TLR8, 9, and 10 mediate pathways of the first immune response to viral infections. Our study reveals that TLRs play a pivotal role in innate immunity associated with renal tissue during the onset of nephrosis.

scholarly journals Roles of Toll-Like Receptors in Nitroxidative Stress in Mammals

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 576 ◽  
Author(s):  
Yao Li ◽  
Shou-Long Deng ◽  
Zheng-Xing Lian ◽  
Kun Yu
Keyword(s):  
Membrane Lipids ◽  
Tissue Injury ◽  
Reactive Oxygen ◽  
Innate Immune ◽  
Cellular Damage ◽  
Inflammatory Factors ◽  
Nitrogen Species ◽  
Toll Like Receptors ◽  
Pathogen Invasion ◽  
Microbial Products

Free radicals are important antimicrobial effectors that cause damage to DNA, membrane lipids, and proteins. Professional phagocytes produce reactive oxygen species (ROS) and reactive nitrogen species (RNS) that contribute towards the destruction of pathogens. Toll-like receptors (TLRs) play a fundamental role in the innate immune response and respond to conserved microbial products and endogenous molecules resulting from cellular damage to elicit an effective defense against invading pathogens, tissue injury, or cancer. In recent years, several studies have focused on how the TLR-mediated activation of innate immune cells leads to the production of pro-inflammatory factors upon pathogen invasion. Here, we review recent findings that indicate that TLRs trigger a signaling cascade that induces the production of reactive oxygen and nitrogen species.

scholarly journals Evidence for an Innate Immune Response in the Immature Human Intestine: Toll-Like Receptors on Fetal Enterocytes

2001 ◽  
Vol 49 (4) ◽  
pp. 589-593 ◽  
Author(s):  
Robert D Fusunyan ◽  
Nanda N Nanthakumar ◽  
Manuel E Baldeon ◽  
W Allan Walker
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Human Intestine ◽  
Toll Like Receptors

scholarly journals Osteoarthritis and Toll-Like Receptors: When Innate Immunity Meets Chondrocyte Apoptosis

Biology ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 65
Author(s):  
Goncalo Barreto ◽  
Mikko Manninen ◽  
Kari K. Eklund
Keyword(s):  
Inflammatory Responses ◽  
Critical Role ◽  
Innate Immune ◽  
Chondrocyte Apoptosis ◽  
Innate Immune Responses ◽  
Toll Like Receptors ◽  
Chondrocyte Death ◽  
Dominant Feature ◽  
Functional Relevance

Osteoarthritis (OA) has long been viewed as a degenerative disease of cartilage, but accumulating evidence indicates that inflammation has a critical role in its pathogenesis. In particular, chondrocyte-mediated inflammatory responses triggered by the activation of innate immune receptors by alarmins (also known as danger signals) are thought to be involved. Thus, toll-like receptors (TLRs) and their signaling pathways are of particular interest. Recent reports suggest that among the TLR-induced innate immune responses, apoptosis is one of the critical events. Apoptosis is of particular importance, given that chondrocyte death is a dominant feature in OA. This review focuses on the role of TLR signaling in chondrocytes and the role of TLR activation in chondrocyte apoptosis. The functional relevance of TLR and TLR-triggered apoptosis in OA are discussed as well as their relevance as candidates for novel disease-modifying OA drugs (DMOADs).

scholarly journals The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between Toll-like receptors

2000 ◽  
Vol 97 (25) ◽  
pp. 13766-13771 ◽  
Author(s):  
A. Ozinsky ◽  
D. M. Underhill ◽  
J. D. Fontenot ◽  
A. M. Hajjar ◽  
K. D. Smith ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Immune System ◽  
Innate Immune System ◽  
Innate Immune ◽  
Toll Like Receptors
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