Instant Blood-mediated Inflammatory Reaction During Islet Transplantation: The Role of Toll-like Receptors Signaling Pathways

Toll-like receptors (TLR) are a group of protein belonging to the family of Pattern Recognition Receptors (PRR) which have the ability to distinguish between an organism's own antigens and foreign ones and to induce immunological response. TLR play a significant part in non-specific immunity but at the same time they are also a vital element linking non-specific response to the specific one. A growing number of data seems to indicate that the non-specific immunity mechanisms affect the development and sustenance of alcohol addiction. Alcohol damages the organism's cells not only directly but also through an increase inintestinal permeability which induces innate immune response of peripheral blood cells. The signaling pathway of Toll-like receptors located on the surface of brain immune cells intensifies the inflammatory reaction and, through modifying gene expression of proinflammatory factors, unnaturally supports it. This overly protracted “sterile inflammatory reaction” positively correlates with alcohol craving affecting also the functioning of the reward system structures and increasing the risk of relapse of alcoholism. Recurrent alcoholic binges sensitize the microglia and cause an escalation in inflammatory reaction which also leads to neurodegeneration. The induction of innate immunity signaling pathways exposes clinical symptoms of alcohol addiction such as increased impulsivity, loss of behavioral control, depressive-anxiety symptoms and cognitive dysfunctions. Traditional methods of treating alcohol addiction have tended to focus predominantly on reducing symptoms which—given the frequency of relapses—seems insufficient. The aim of the present paper is to discuss the role of toll-like receptors as elements of the immunity system which, together with the nervous system, plays a crucial part in the pathogenesis of alcohol addiction. We also wish to present pharmacotherapeutic perspectives targeted at the neuroimmunological mechanisms of alcohol addiction.

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The significance of Toll-like receptors in selected nephropathies

Diagnostyka Laboratoryjna ◽

10.5604/01.3001.0013.7445 ◽

2019 ◽

Vol 55 (2) ◽

pp. 107-112

Author(s):

Sebastian Mertowski ◽

Ewelina Grywalska ◽

Jarosław Ludian ◽

Agnieszka Grafka ◽

Barbara Pęksa ◽

...

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

Inflammatory Reaction ◽

Inflammatory Mediators ◽

Modern Society ◽

Kidney Damage ◽

Toll Like Receptors ◽

Molecular Patterns ◽

Stimulation Of

The diseases associated with kidney damage are an increasingly common problem in modern society and complications of chronic renal failure can result in death. Research conducted by many scientific centers, both Polish and foreign, concern the search for possible factors involved in the pathogenesis of glomerulonephritis. One of the possible causes of nephropathy may include the dysfunction of Toll-like receptors (TLRs), which constitute a “bridge” between innate and acquired response. TLRs are involved in receiving signals related to pathogen associated molecular patterns (PAMPs) as well as receiving information related to the danger associated molecular patterns (DAMP). The stimulation of these receptors activates a cascade of reactions in the course of which various mediators, including pro-inflammatory mediators, are produced. The resulting long-lasting inflammation that develops within the glomerulus may cause kidney damage. In both nephropathies caused by excessive production of antibodies in the IgA class, as well as nephropathy induced by diabetes or lupus, the expression of individual TLRs may indicate an inducer of an inflammatory reaction cascade that leads to kidney damage. This article focuses on literature reports that present current views on the role of TLRs in the pathogenesis of the most common nephropathies.

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Toll-like Receptors Signaling Pathways as a Potential Therapeutic Target in Cardiovascular Disease

Current Pharmaceutical Design ◽

10.2174/1381612824666180614090224 ◽

2018 ◽

Vol 24 (17) ◽

pp. 1887-1898 ◽

Cited By ~ 9

Author(s):

Seyed Mostafa Parizadeh ◽

Maryam Ghandehari ◽

Motahareh Heydari-majd ◽

Sima Seifi ◽

Ramin Mardani ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiovascular Disease ◽

Immune System ◽

Signaling Pathways ◽

Cardiac Remodeling ◽

Therapeutic Target ◽

Good Evidence ◽

Toll Like Receptors ◽

Potential Therapeutic Target

Cardiovascular Disease (CVD) is one of the most important causes of morbidity and mortality, and associated with an important economic burden globally. Over the last decade, the prevalence of CVD has been rising globally, and is now associated with millions of death annually in both developed and developing countries. There is good evidence that the immune system is involved in the pathophysiology of CVD. Toll-like receptors (TLRs) and their down-stream signaling pathways play an important role in the immune system. Recent studies have suggested that the TLRs are involved in atherogenesis, including stroke, myocardial infarction, ischemiareperfusion injury, cardiac remodeling and development of Heart Failure (HF). In this review we have summarized the recent studies investigating the role of TLRs in CVD and the potential for using TLRs signaling pathways as a therapeutic target in CVD.

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