scholarly journals The Dual Role of Toll-like Receptor10

2021 ◽  
Author(s):  
Motahareh Dargahi ◽  
Niloufar Taheri ◽  
Zahra Mirsanei ◽  
Arezoo Rasti ◽  
Reza Jafari
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Human Cancer ◽  
Primary Response ◽  
Mitogen Activated Protein Kinase ◽  
Regulatory Function ◽  
Anti Inflammatory

Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) family that identify pathogen-associated molecular patterns derived from microbes and activate immune cell response. Following TLRs ligation, different adaptor and transcription molecules such as myeloid differentiation primary response gene 88 (MyD88) and nuclear factor kappa B (NF-kB) are recruited that initiate inflammatory signaling pathways. The human Toll-like receptor 10 (hTLR10) is a novel member of the PRRs family with a regulatory function of immune responses because of unique cytoplasmic domains which lead to induction of both inflammatory and anti-inflammatory properties. Recent studies have reported the association of TLR10 polymorphisms with many inflammatory diseases and human cancer. Engagement of TLR10 on the surface of the epithelium and macrophages leads to the production of proinflammatory cytokines and chemokines, while other studies have proven an anti-inflammatory role of TLR10. Accordingly, TLR10 suppresses proinflammatory cytokine production via negative regulation of MyD88 and the Akt (protein kinase B) and MAPK (mitogen-activated protein kinase) signaling pathways. This review aimed to provide answers for these conflicting findings (Inflammatory and anti-inflammatory properties of TLR10) to further identify distinct biological functions of TLR10.

scholarly journals The Immunomodulatory and Anti-Inflammatory Role of Polyphenols

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1618 ◽  
Author(s):  
Nour Yahfoufi ◽  
Nawal Alsadi ◽  
Majed Jambi ◽  
Chantal Matar
Keyword(s):  
Protein Kinase ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Biologically Active ◽  
Mitogen Activated Protein Kinase ◽  
Clear Understanding ◽  
Akt Inhibitor ◽  
Amino Terminal ◽  
Anti Inflammatory ◽  
Arachidonic Acids

This review offers a systematic understanding about how polyphenols target multiple inflammatory components and lead to anti-inflammatory mechanisms. It provides a clear understanding of the molecular mechanisms of action of phenolic compounds. Polyphenols regulate immunity by interfering with immune cell regulation, proinflammatory cytokines’ synthesis, and gene expression. They inactivate NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and modulate mitogen-activated protein Kinase (MAPk) and arachidonic acids pathways. Polyphenolic compounds inhibit phosphatidylinositide 3-kinases/protein kinase B (PI3K/AkT), inhibitor of kappa kinase/c-Jun amino-terminal kinases (IKK/JNK), mammalian target of rapamycin complex 1 (mTORC1) which is a protein complex that controls protein synthesis, and JAK/STAT. They can suppress toll-like receptor (TLR) and pro-inflammatory genes’ expression. Their antioxidant activity and ability to inhibit enzymes involved in the production of eicosanoids contribute as well to their anti-inflammation properties. They inhibit certain enzymes involved in reactive oxygen species ROS production like xanthine oxidase and NADPH oxidase (NOX) while they upregulate other endogenous antioxidant enzymes like superoxide dismutase (SOD), catalase, and glutathione (GSH) peroxidase (Px). Furthermore, they inhibit phospholipase A2 (PLA2), cyclooxygenase (COX) and lipoxygenase (LOX) leading to a reduction in the production of prostaglandins (PGs) and leukotrienes (LTs) and inflammation antagonism. The effects of these biologically active compounds on the immune system are associated with extended health benefits for different chronic inflammatory diseases. Studies of plant extracts and compounds show that polyphenols can play a beneficial role in the prevention and the progress of chronic diseases related to inflammation such as diabetes, obesity, neurodegeneration, cancers, and cardiovascular diseases, among other conditions.

scholarly journals In Vivo Role of p38 Mitogen-Activated Protein Kinase in Mediating the Anti-inflammatory Effects of CpG Oligodeoxynucleotide in Murine Asthma

2002 ◽  
Vol 169 (10) ◽  
pp. 5955-5961 ◽  
Author(s):  
Barun K. Choudhury ◽  
James S. Wild ◽  
Rafeul Alam ◽  
Dennis M. Klinman ◽  
Istvan Boldogh ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Cpg Oligodeoxynucleotide ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Role of signaling pathway in biological cause of Rheumatoid arthritis

2020 ◽  
Vol 12 ◽  
Author(s):  
Rakesh Kumar Chauhan ◽  
Pramod Kumar Sharma ◽  
Shikha Srivastava
Keyword(s):  
Rheumatoid Arthritis ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Interleukin 1 ◽  
Development Stage ◽  
The Body ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Heart Blood

Abstract:: Rheumatoid Arthritis is a chronic progressive inflammatory auto-immune disease in which the immune system of the body attacks its cartilage and joints lining. It not only affects synovial joints but also many other sites including heart, blood vessels, and skins. It is more common in females than in males. The exact cause of rheumatoid arthritis is not well established but the hypothesis reported in the literature is that in the development stage of the disease, both genetics and environmental factors can play an inciting role. Along with these factors alteration in the normal physiology of enzymatic action, acts as a trigger to develop this condition. Numerous signaling pathways involved in the pathogenesis of Rheumatoid Arthritis involves activation of mitogen-activated protein kinase, kinases Janus family, P-38 Mitogen-Activated Protein Kinase, Nuclear Factor-kappa B. Interleukin-1 to play a proinflammatory cytokine that plays an important role in inflammation in RA. These are also associated with an increase in neutrophil, macrophage and lymphocytic chemotaxis, mast cell degranulation, activation, maturation and survival of T-cells and B-cells activated. These signaling pathways also show that p38α downregulation in myeloid cells exacerbates the severity of symptoms of arthritis. Thus, present review carters about the detail of different signaling pathways and their role in rheumatoid arthritis.

Novel Therapeutic Potential of Mitogen-Activated Protein Kinase Activated Protein Kinase 2 (MK2) in Chronic Airway Inflammatory Disorders

2019 ◽  
Vol 20 (4) ◽  
pp. 367-379 ◽  
Author(s):  
Rakesh Kumar Singh ◽  
Abul Kalam Najmi
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Critical Factor ◽  
Mitogen Activated Protein Kinase ◽  
Inflammatory Conditions ◽  
Targeted Inhibition ◽  
Chronic Airway

Objective: The primary focus of this review is to highlight the current and emerging proinflammatory role of MK2 kinase signaling in p38MAPK pathway and to provide a detailed evaluation on the prospects of MK2 inhibition with special emphasis on the etiology of chronic inflammatory airway diseases, such as asthma, idiopathic pulmonary fibrosis, lung cancer, acute lung injury and acute respiratory distress syndrome. Background: MK2 belongs to serine-threonine kinase family and is activated directly by stress and inflammatory signal through p38MAPK phosphorylation in diverse inflammatory conditions through the Toll-like receptor signaling pathway. MK2 has been thought to be a critical factor involved in the regulation of synthesis and release of pro-inflammatory (TNF-α, IL-6 and IL-1β, etc.) proteins. Targeted inhibition of MK2 kinase has been shown to significantly reduce the production and release of these cytokine molecules. Therefore, MK2 has been identified as an effective strategy (alternative to p38MAPK) to block this pro-inflammatory signaling pathway. Results: The inhibition of MK2 may lead to similar or better efficacy as that of p38 inhibitors, and interestingly avoids the systemic toxicity shown by the p38 inhibitors. Thus, MK2 has been the focus of intense interdisciplinary research and its specific inhibition can be a novel and potential therapeutic strategy for the treatment of chronic airway inflammatory diseases. Conclusion: Promising advancement in understanding and rigorous exploration of the role of MK2 kinase in inflammatory processes may contribute to the development of newer and safer therapy for the treatment of chronic airway inflammatory diseases in the future.

scholarly journals Network pharmacology analysis of ZiShenWan for diabetic nephropathy and experimental verification of its anti-inflammatory mechanism

2020 ◽  
Author(s):  
Xiaoyuan Guo ◽  
You Wu ◽  
Chengfei Zhang ◽  
Lili Wu ◽  
Lingling Qin ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Protein Kinase ◽  
Inflammatory Response ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Mitogen Activated Protein Kinase ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Anti Inflammatory

Abstract Background: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). The inflammatory response plays a critical role in the process of DN. ZiShenWan (ZSW) is a classical Chinese medicinal formula with remarkable clinical therapeutic effects on DN, but its pharmacological action mechanisms remain unclear. Methods: In this study, a network pharmacology approach was applied to investigate the pharmacological mechanism of ZSW in DN therapy. The “drug-ingredient-target” network for ZSW in DN treatment was established with Cytoscape software based on candidate active components of ZSW and targets in DN treatment obtained from databases. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed with the key targets. Because inflammation is important in DN, the key targets and signaling pathways associated with the anti-inflammatory, renoprotective mechanism of ZSW were partially validated in db/db mice. Results: A total of 56 active ingredients in ZSW and 166 DN-related targets were selected from databases. Various related genes and pathways participate in the inflammatory response. ZSW markedly alleviated renal injury in db/db mice by inhibiting the exaggerated release of proinflammatory cytokines such as interleukin (IL)-1β, IL-6, tumor necrosis factor -ɑ (TNF-ɑ), monocyte chemotactic protein-1 (MCP-1) and transforming growth factor-β1 (TGF-β1) and regulating the p38 mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase-protein kinase B (PI3K-Akt) signaling pathways. Conclusions: Network pharmacology analysis demonstrated that ZSW achieved therapeutic renoprotective effects in DN by alleviating the inflammatory response via regulation of multiple targets and signaling pathways.

Berberine hydrochloride protects against cytokine-induced inflammation through multiple pathways in undifferentiated C2C12 myoblast cells

2019 ◽  
Vol 97 (8) ◽  
pp. 699-707 ◽  
Author(s):  
Anil Poudel ◽  
Joseph Yi Zhou ◽  
Naveen Mekala ◽  
Ryan Welchko ◽  
Mariana Georgeta Rosca ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Metabolic Syndrome ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Mitogen Activated Protein Kinase ◽  
C2c12 Myoblast ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory ◽  
Myoblast Cells

Obesity is associated with skeletal muscle insulin resistance and the development of metabolic syndrome. Undifferentiated skeletal muscle cells are sensitive to oxidative stress. Berberine hydrochloride (BBR) improves insulin resistance and exhibits anti-inflammatory properties. However, the underlying mechanism and the cell signaling pathways involved remain largely elusive. We therefore investigated the anti-inflammatory effects of BBR and the signaling pathways using skeletal C2C12 myoblast cells. Undifferentiated C2C12 myoblast cells were treated with interleukin-1β alone or in combination with tumor necrosis factor-α in the presence or absence of BBR. We found that BBR reduced the cytokine-induced expression of inducible nitric oxide synthase and stress-related kinases including p-38 mitogen-activated protein kinase, nuclear factor kappa B (NF-κB), and stress-activated protein kinases/Jun amino-terminal kinases (SAPK/JNK) in C2C12 myoblast cells. Furthermore, BBR reversed cytokine-mediated suppression of AMP-activated protein kinase (AMPKα), sirtuin-1 (SIRT-1), and PPAR-γ coactivator-1α (PGC-1α). In addition, cytokine-induced reduction of mitochondrial marker proteins and function were rescued after BBR treatment. Catalase, an antioxidant enzyme, was elevated after BBR treatment. Our results demonstrate that BBR ameliorates cytokine-induced inflammation. The anti-inflammatory effect of BBR in skeletal progenitor cells is mediated through pathways including activation of the AMPKα-SIRT-1-PGC-1α, inhibition of the mitogen-activated protein kinase 4 (MKK4)-SAPK/JNK-C-JUN, as well as protection of mitochondrial bioenergetics. BBR may be a potential medication for metabolic syndrome.

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