TLR 4 / MD2 Complex inhibitors potential therapeutic prospective for asthma and asthma exacerbation

2021 ◽  
Vol 16 (11) ◽  
pp. 164-176
Author(s):  
Swamita Arora ◽  
Tanveer Naved ◽  
Sanjar Alam ◽  
Bhupendra Chauhan ◽  
Harikesh Kalonia
Keyword(s):  
Initial Step ◽  
Cardiovascular Disorder ◽  
The Body ◽  
Innate And Adaptive Immunity ◽  
Cytokines And Chemokines ◽  
Asthma Patients ◽  
Tlr4 Activation ◽  
Molecular Patterns ◽  
Tlr Signalling ◽  
Inflammatory Effect

The feedback of our body to foreign particles is initially initiated by the innate immunity where the likes Toll- Like Receptors (TLRs), play an important role in the identification process. The identification of the trouble through the interaction of the receptor is the initial step to propagate the protective agents throughout the body. These interact action with the attacking pathogens like viruses and bacteria (PAMPs, pathogen-associated molecular patterns) or substances produced cells of the body which are injured (DAMPs, danger-associated molecular patterns) helping in the identification. However, the innate and adaptive immunity of both of them gets stimulated through the release of various substances such as cytokines and chemokines due to TLR activation. In part of the progress, many reports have been identified as the activation of the TLR4 complex, a receptor of the innate immune system that may underpin the pathophysiology of many human diseases including asthma, cardiovascular disorder, diabetes, obesity, metabolic syndrome, autoimmune disorders, neuroinflammatory and psychiatric disorders. Substances of synthetic and natural origin have been discussed here and have been found to produce the anti-inflammatory effect by targeting pathways of TLR4 activation. In the present review, our focus is to develop a conclusion about the TL4 complex inhibition for the betterment of asthma patients and combine the reports about the progressing of TLR signalling pathway modulators.

Immune and Metabolic Interactions of Human Erythrocytes: A Molecular Perspective

2020 ◽  
Vol 20 ◽  
Author(s):  
Charalampos Papadopoulos ◽  
Maria Panopoulou ◽  
Konstantinos Anagnostopoulos ◽  
Ioannis Tentes
Keyword(s):  
Immune Regulation ◽  
The Body ◽  
Main Function ◽  
Oxygen Carriers ◽  
Bioactive Lipids ◽  
Innate And Adaptive Immunity ◽  
Surface Molecules ◽  
Metabolic Interactions ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Background: Apart from their main function as oxygen carriers in vertebrates, erythrocytes are also involved in immune regulation. By circulating throughout the body, the erythrocytes are exposed and interact with tissues that are damaged as a result of a disease. Methods: In this study, we summarize the literature regarding the contribution of erythrocytes to immune regulation and metabolism. Results: Under the circumstances of a disease state, the erythrocytes may lose their antioxidant capacity and release Damage Associated Molecular Patterns, resulting in regulation of innate and adaptive immunity. In addition, the erythrocytes scavenge and affect the levels of chemokines, circulating cell-free mtDNA and C3b attached immune complexes. Furthermore, through surface molecules, erythrocytes control the function of T lymphocytes, macrophages and dendritic cells. Through an array of enzymes, red blood cells contribute to the pool of blood’s bioactive lipids. Finally, the erythrocytes contribute to reverse cholesterol transport, through various mechanisms. Conclusion: Our study is highlighting overlooked molecular interactions between erythrocytes and immunity and metabolism, which could lead to the discovery of potent therapeutic targets for immunometabolic diseases.

scholarly journals Natural Products with Toll-Like Receptor 4 Antagonist Activity

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Monica Molteni ◽  
Annalisa Bosi ◽  
Carlo Rossetti
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Toll Like Receptor ◽  
Antagonist Activity ◽  
Toll Like Receptor 4 ◽  
Cytokines And Chemokines ◽  
Inflammatory Processes ◽  
Tlr4 Activation ◽  
Activation Pathways ◽  
Molecular Patterns

Toll-Like Receptors (TLRs) are the innate immunity receptors that play an activating role when interacting with molecules released by bacteria and viruses (PAMPs, pathogen-associated molecular patterns) or with molecules released by injured cells and tissues (DAMPs, danger-associated molecular patterns). TLR triggering leads to the induction of proinflammatory cytokines and chemokines, driving the activation of both innate and adaptive immunity. In particular, Toll-Like Receptor 4 (TLR4) has been described to be involved in the inflammatory processes observed in several pathologies (such as ischemia/reperfusion injury, neuropathic pain, neurodegenerative diseases, and cancer). Molecules obtained by natural sources have been discovered to exert an anti-inflammatory action by targeting TLR4 activation pathways. This review focuses on TLR4 antagonists obtained from bacteria, cyanobacteria, and plants.

Targeting Toll like Receptors in Cancer: Role of TLR Natural and Synthetic Modulators

2020 ◽  
Vol 26 (39) ◽  
pp. 5040-5053 ◽  
Author(s):  
Arunaksharan Narayanankutty ◽  
Aswathi Sasidharan ◽  
Joice T. Job
Keyword(s):  
Immune Response ◽  
Web Of Science ◽  
Broad Class ◽  
The Body ◽  
Toll Like Receptors ◽  
Transmembrane Receptors ◽  
Molecular Patterns ◽  
Tlr Signalling ◽  
Detailed Outline

Background: Toll like receptors (TLRs) are a group of transmembrane receptors belonging to the broad class pattern recognition receptors (PRR), involved in recognition of Pathogen Associated Molecular Patterns (PAMPs) thereby inducing an immune response. Apart from these exogenous PAMPs, numerous endogenous PAMPs are also ligands for various TLRs thereby activating the TLR dependent immune response, subsequently leading to the onset of an inflammatory response. Prolonged activation of TLR by these endogenous PAMPs leads to chronic inflammatory insults to the body and which in turn alters the proliferative patterns of the cells, which ultimately leads to the development of cancer. Objectives: The present review aims to provide a detailed outline of the differential roles of various TLRs in cancer and the possible use of them as a therapeutic target. Methods: Data were collected from PubMed/Sciencedirect/Web of Science database and sorted; the latest literature on TLRs was incorporated in the review. Results: Among the different TLRs, few are reported to be anti-neoplastic, which controls the cell growth and multiplication in response to the endogenous signals. On the contrary, numerous studies have reported the procarcinogenic potentials of TLRs. Hence, TLRs have emerged as a potential target for the prevention and treatment of various types of cancers. Several molecules, such as monoclonal antibodies, small molecule inhibitors and natural products have shown promising anticancer potential by effectively modulating the TLR signalling. Conclusion: Toll-like receptors play vital roles in the process of carcinogenesis, hence TLR targeting is a promising approach for cancer prevention.

scholarly journals Involvement of Probiotics and Postbiotics in the Immune System Modulation

Biologics ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 89-110
Author(s):  
Neslihan Yeşilyurt ◽  
Birsen Yılmaz ◽  
Duygu Ağagündüz ◽  
Raffaele Capasso
Keyword(s):  
Immune System ◽  
Pharmaceutical Industry ◽  
Intestinal Microbiota ◽  
Health Benefits ◽  
The Body ◽  
Future Research ◽  
Immune Systems ◽  
Advantages And Disadvantages ◽  
Immune System Modulation ◽  
Molecular Patterns

Intestinal microbiota interacts with other systems, especially the immune system, which is responsible for protecting the body by recognizing “stranger” (pathogen associated molecular patterns-PAMPs) and “danger” (damage-associated molecular patterns-DAMPs) molecular motifs. In this manner, it plays an important role in the pathogenesis of various diseases and health. Despite the use of probiotics that modulate the intestinal microbiota in providing health benefits and in the treatment of diseases, there are some possible concerns about the possibility of developing adverse effects, especially in people with suppressed immune systems. Since probiotics provide health benefits with bioactive compounds, studies are carried out on the use of products containing non-living probiotic microorganisms (paraprobiotics) and/or their metabolites (postbiotics) instead of probiotic products. It is even reported that these microbial compounds have more immunomodulatory activities than living microorganisms via some possible mechanism and eliminates some disadvantages of probiotics. Considering the increasing use of functional foods in health and disease, further studies are needed with respect to the benefits and advantages of parabiotic and/or postbiotic use in the food and pharmaceutical industry as well as immune system modulation. Although probiotics have been extensive studied for a long time, it seems that postbiotics are promising tools for future research and applications according to the recent literature. This review aimed to evaluate the interaction of probiotics and postbiotics with the immune systems and also their advantages and disadvantages in the area of food-pharmaceutical industry and immune system modulation.

scholarly journals TRIM31 facilitates K27-linked polyubiquitination of SYK to regulate antifungal immunity

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xueer Wang ◽  
Honghai Zhang ◽  
Zhugui Shao ◽  
Wanxin Zhuang ◽  
Chao Sui ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Fungal Pathogen ◽  
Essential Role ◽  
Molecular Mechanisms ◽  
Systemic Infection ◽  
Lectin Receptors ◽  
Innate And Adaptive Immunity ◽  
Cytokines And Chemokines

AbstractSpleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase, which plays an essential role in both innate and adaptive immunity. However, the key molecular mechanisms that regulate SYK activity are poorly understood. Here we identified the E3 ligase TRIM31 as a crucial regulator of SYK activation. We found that TRIM31 interacted with SYK and catalyzed K27-linked polyubiquitination at Lys375 and Lys517 of SYK. This K27-linked polyubiquitination of SYK promoted its plasma membrane translocation and binding with the C-type lectin receptors (CLRs), and also prevented the interaction with the phosphatase SHP-1. Therefore, deficiency of Trim31 in bone marrow-derived dendritic cells (BMDCs) and macrophages (BMDMs) dampened SYK-mediated signaling and inhibited the secretion of proinflammatory cytokines and chemokines against the fungal pathogen Candida albicans infection. Trim31−/− mice were also more sensitive to C. albicans systemic infection than Trim31+/+ mice and exhibited reduced Th1 and Th17 responses. Overall, our study uncovered the pivotal role of TRIM31-mediated K27-linked polyubiquitination on SYK activation and highlighted the significance of TRIM31 in anti-C. albicans immunity.

scholarly journals Dietary Fiber's Effect on High Sensitivity C-reactive Protein Serum in Sedentary Workers

2021 ◽  
Vol 5 (1) ◽  
pp. 40
Author(s):  
Livia Kurniati Saputra ◽  
Dian Novita Chandra ◽  
Ninik Mudjihartini
Keyword(s):  
Body Weight ◽  
High Sensitivity ◽  
The Body ◽  
Low Grade ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Dietary Fiber Intake ◽  
Anti Inflammatory ◽  
Low Grade Inflammation ◽  
Inflammatory Effect

Low grade inflammation has been recognized of being involved in the pathogenesis of chronic disease pandemic. Individual lifestyle plays a major role in the development of low grade inflammation. Sedentary workers are at risk of low grade inflammation due to the nature of their work. Dietary habit also contributes to inflammatory status in the body. Dietary fiber intake indirectly affects the immune system. It has been hypothesized that fiber has anti-inflammatory effects, both body weight-related and body weight-unrelated This review will focus more on body weight-unrelated anti-inflammatory effect of fiber, especially through fiber’s fermentation metabolites, the short chain fatty acid (SCFA). Its anti-inflammatory effect can be seen by monitoring a biomarker of inflammation in the body, the high sensitivity C-reactive protein (hsCRP). This review’s objective is to cover the mechanisms and role of dietary fiber intake on serum hsCRP level as a marker of low grade inflammation on sedentary workers. 

scholarly journals The Role of Toll-Like Receptor 4 in Infectious and Noninfectious Inflammation

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Monica Molteni ◽  
Sabrina Gemma ◽  
Carlo Rossetti
Keyword(s):  
Tissue Injury ◽  
Sterile Inflammation ◽  
Research Progress ◽  
Toll Like Receptor ◽  
Proinflammatory Response ◽  
Toll Like Receptor 4 ◽  
The Family ◽  
Tlr4 Activation ◽  
Molecular Patterns

Toll-like receptor 4 (TLR4) belongs to the family of pattern recognition receptors (PRRs). They are highly conserved receptors that recognize conserved pathogen-associated molecular patterns (PAMPs), thus representing the first line of defense against infections. TLR4 has been long recognized as the sensing receptor for gram-negative lipopolysaccharide (LPS). In addition, it also binds endogenous molecules produced as a result of tissue injury. Hence, TLR4 represents a key receptor on which both infectious and noninfectious stimuli converge to induce a proinflammatory response. TLR4-mediated inflammation, triggered by exogenous or endogenous ligands, is also involved in several acute and chronic diseases, having a pivotal role as amplifier of the inflammatory response. This review focuses on the research progress about the role of TLR4 activation in infectious and noninfectious (e.g., sterile) inflammation and the effects of TLR4 signaling in some pathological conditions.

Evaluation of effect of efficacy of Koshtha Shuddhi in the Management of Gridrasi (Sciatica)

The Healer ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 48-51
Author(s):  
Sandeepanie Maragalawaththa ◽  
E.R.H.S.S. Ediriweera
Keyword(s):  
Medical Condition ◽  
The Body ◽  
Root Cause ◽  
Lower Back ◽  
Effect Of Therapy ◽  
Chief Complaints ◽  
Group A ◽  
Group B ◽  
Gastro Intestinal Tract ◽  
Inflammatory Effect

Introduction: Sciatica is a medical condition of pain going down the leg through back, outside, or front of the leg from the lower back. It can be co-related with Grdrasi caused by both the aggravated Vata and Kapha two elements out of three basic elements of the body. Diagnostic method of disease is different and management also based on root cause of the disease. Sepalika  (Nyctanthes arbor-tristis.Linn.)(Oleacea) leaves are having anti inflammatory effect and analgesic effect. Aim and Objectives: To Evaluate the efficacy of Koshtha (GIT) (Gastro Intestinal tract) Shuddhi (Purification) in the management of Gridrasi w.s.r. to Sciatica. Material and methods: For this study, 20 patients were resisted and divided into two groups. Registered patients of group A and Group B were given Koshtha Shuddhi with Sepalika leaves decoction along with Sashapadi oil Abhyanga and Sand Potali fomentation and Sepalika leaves decoction along with Sashapadi oil Abhyanga and Sand Potali fomentation respectively for 2 weeks before meal. Patients of group A were given 120ml of Vasagudushi decoction with 5ml Eranada oil twice a day for purpose of Koshtha Shuddhi for 3 days. The effect of therapy was evaluated on the basis of changes of chief complaints and SLR test was taken for assessment parameter. Discussion: The statistically significant relief was showed on the chief complaints of Gridrasi (Sciatica) in the both the groups except Ruk (Pain) in group B. SLR of all the patient of present study were in between 30o- 70o in R/side LL (Lower Limb). SLR was changed of both the groups up to 70o-90o and 100% showed relief except 4 patients in the group B. Conclusion: It can be concluded that the Koshtha Shuddhi is showed comparatively better effect than management of Gridrasi (Sciatica) without carried out Koshtha Shuddhi.

scholarly journals n-3 PUFA and obesity: from peripheral tissues to the central nervous system

2018 ◽  
Vol 119 (11) ◽  
pp. 1312-1323 ◽  
Author(s):  
Aline Haas de Mello ◽  
Marcela Fornari Uberti ◽  
Bianca Xavier de Farias ◽  
Nathalia Alberti Ribas de Souza ◽  
Gislaine Tezza Rezin
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cardiac Arrhythmias ◽  
The Body ◽  
Low Grade ◽  
Therapeutic Approaches ◽  
Peripheral Tissues ◽  
Inflammatory State ◽  
The Central Nervous System ◽  
Inflammatory Effect

AbstractThe current paradigms of prevention and treatment are unable to curb obesity rates, which indicates the need to explore alternative therapeutic approaches. Obesity leads to several damages to the body and is an important risk factor for a number of other chronic diseases. Furthermore, despite the first alterations in obesity being observed and reported in peripheral tissues, studies indicate that obesity can also cause brain damage. Obesity leads to a chronic low-grade inflammatory state, and the therapeutic manipulation of inflammation can be explored. In this context, the use of n-3 PUFA (especially in the form of fish oil, rich in EPA and DHA) may be an interesting strategy, as this substance is known by its anti-inflammatory effect and numerous benefits to the body, such as reduction of TAG, cardiac arrhythmias, blood pressure and platelet aggregation, and has shown potential to help treat obesity. Thereby, the aim of this narrative review was to summarise the literature related to n-3 PUFA use in obesity treatment. First, the review provides a brief description of the obesity pathophysiology, including alterations that occur in peripheral tissues and at the central nervous system. In the sequence, we describe what are n-3 PUFA, their sources and their general effects. Finally, we explore the main topic linking obesity and n-3 PUFA. Animal and human studies were included and alterations on the whole organism were described (peripheral tissues and brain).

scholarly journals Broad and direct interaction between TLR and Siglec families of pattern recognition receptors and its regulation by Neu1

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Guo-Yun Chen ◽  
Nicholas K Brown ◽  
Wei Wu ◽  
Zahra Khedri ◽  
Hai Yu ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Direct Interaction ◽  
Pattern Recognition Receptors ◽  
Immunoglobulin Superfamily ◽  
Lectin Receptors ◽  
Sialidase Inhibitor ◽  
Tlr4 Ligand ◽  
Tlr4 Activation ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Both pathogen- and tissue damage-associated molecular patterns induce inflammation through toll-like receptors (TLRs), while sialic acid-binding immunoglobulin superfamily lectin receptors (Siglecs) provide negative regulation. Here we report extensive and direct interactions between these pattern recognition receptors. The promiscuous TLR binders were human SIGLEC-5/9 and mouse Siglec-3/E/F. Mouse Siglec-G did not show appreciable binding to any TLRs tested. Correspondingly, Siglece deletion enhanced dendritic cell responses to all microbial TLR ligands tested, while Siglecg deletion did not affect the responses to these ligands. TLR4 activation triggers Neu1 translocation to cell surface to disrupt TLR4:Siglec-E interaction. Conversely, sialidase inhibitor Neu5Gc2en prevented TLR4 ligand-induced disruption of TLR4:Siglec E/F interactions. Absence of Neu1 in hematopoietic cells or systematic treatment with sialidase inhibitor Neu5Gc2en protected mice against endotoxemia. Our data raised an intriguing possibility of a broad repression of TLR function by Siglecs and a sialidase-mediated de-repression that allows positive feedback of TLR activation during infection.

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