Tribbles and arthritis: what are the links?

2015 ◽  
Vol 43 (5) ◽  
pp. 1051-1056 ◽  
Author(s):  
Andrew D. Rowan ◽  
Gary J. Litherland
Keyword(s):  
Rheumatoid Arthritis ◽  
Current Knowledge ◽  
Cell Signalling ◽  
Cartilage Destruction ◽  
Signalling Pathways ◽  
Signal Transduction Pathways ◽  
Intracellular Protein ◽  
Cellular Mechanisms ◽  
Intracellular Protein Degradation ◽  
The Impact

The pseudo-kinase family of tribbles (TRIB) proteins has been linked to a variety of cell signalling pathways and appears to have functionally divergent roles with respect to intracellular protein degradation and the ability to regulate signal transduction pathways. In the arthritides, inflammation and a wide variety of pro-inflammatory pathways have been implicated to drive the cartilage destruction and consequent disability associated with both rheumatoid arthritis (RA) and osteoarthritis (OA). Despite burgeoning evidence linking the TRIB to inflammation-related pathologies such as diabetes, multiple sclerosis and cancer, very little is known about their roles in arthritis. The present review discusses current knowledge of the impact of TRIB on pro-inflammatory cellular mechanisms and pathways known to be important in the pathogenesis of RA and OA.

scholarly journals The Joint-Brain Axis: Insights From Rheumatoid Arthritis on the Crosstalk Between Chronic Peripheral Inflammation and the Brain

2020 ◽  
Vol 11 ◽  
Author(s):  
Patrick Süß ◽  
Tobias Rothe ◽  
Alana Hoffmann ◽  
Johannes C. M. Schlachetzki ◽  
Jürgen Winkler
Keyword(s):  
Rheumatoid Arthritis ◽  
Current Knowledge ◽  
Later Life ◽  
Chronic Inflammatory Disease ◽  
Peripheral Inflammation ◽  
Cellular Mechanisms ◽  
Increased Risk ◽  
Neuropsychiatric Diseases ◽  
Patients At Risk ◽  
The Impact

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by erosive polyarthritis. Beyond joint pathology, RA is associated with neuropsychiatric comorbidity including depression, anxiety, and an increased risk to develop neurodegenerative diseases in later life. Studies investigating the central nervous system (CNS) in preclinical models of RA have leveraged the understanding of the intimate crosstalk between peripheral and central immune responses. This mini review summarizes the current knowledge of CNS comorbidity in RA patients and known underlying cellular mechanisms. We focus on the differential regulation of CNS myeloid and glial cells in different mouse models of RA reflecting different patterns of peripheral immune activation. Moreover, we address CNS responses to anti-inflammatory treatment in human RA patients and mice. Finally, to illustrate the bidirectional communication between the CNS and chronic peripheral inflammation, we present the current knowledge about the impact of the CNS on arthritis. A comprehensive understanding of the crosstalk between the CNS and chronic peripheral inflammation will help to identify RA patients at risk of developing CNS comorbidity, setting the path for future therapeutic approaches in both RA and neuropsychiatric diseases.

scholarly journals Versatility of USP18 in physiology and pathophysiology

2019 ◽  
Author(s):  
Paulina Dziamałek-Macioszczyk ◽  
Joanna Haraźna ◽  
Tomasz Stompór
Keyword(s):  
Bacterial Infections ◽  
Current Knowledge ◽  
Cell Signalling ◽  
Signalling Pathways ◽  
Type I ◽  
Multifunctional Protein ◽  
Enzymatic Function ◽  
Multiple Processes ◽  
Specific Protease ◽  
Interferon Stimulated Gene 15

Ubiquitin-specific peptidase 18 (USP18) is a multifunctional protein and its roles are still being investigated. This enzyme removes ubiquitin-like molecules from their substrates and the only known interferon-stimulated gene 15 (ISG15) specific protease. Apart from its enzymatic function, it also inhibits interferon type I and III signalling pathways. USP18 is known to regulate multiple processes, such as: cell cycle, cell signalling and response to viral and bacterial infections. Moreover, it contributes to the development of several autoimmune diseases and carcinogenesis, and recently was described as a cardiac remodelling inhibitor. This review summarizes the current knowledge on USP18 functions, highlighting its contribution to the development of heart failure, given the fact that this disease’s etiology is now considered to be inflammatory in nature.

scholarly journals Beverages in Rheumatoid Arthritis: What to Prefer or to Avoid

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3155 ◽  
Author(s):  
Mrinalini Dey ◽  
Maurizio Cutolo ◽  
Elena Nikiphorou
Keyword(s):  
Rheumatoid Arthritis ◽  
Patient Management ◽  
Current Knowledge ◽  
Signalling Pathways ◽  
Main Body ◽  
Future Studies ◽  
Downstream Effects ◽  
Controversial Topic ◽  
Diet And Lifestyle

Background: The role of nutrition in the pathogenesis of rheumatic diseases, including rheumatoid arthritis (RA), has gained increasing attention in recent years. A growing number of studies have focussed on the diverse nutritional contents of beverages, and their possible role in the development and progression of RA. Main body: We aimed to summarise the current knowledge on the role of a range of beverages in the context of RA. Beverages have a key role within the mosaic of autoimmunity in RA and potential to alter the microbiome, leading to downstream effects on inflammatory pathways. The molecular contents of beverages, including coffee, tea, and wine, have similarly been found to interfere with immune signalling pathways, some beneficial for disease progression and others less so. Finally, we consider beverages in the context of wider dietary patterns, and how this growing body of evidence may be harnessed by the multidisciplinary team in patient management. Conclusions: While there is increasing work focussing on the role of beverages in RA, integration of discussions around diet and lifestyle in our management of patients remains sparse. Nutrition in RA remains a controversial topic, but future studies, especially on the role of beverages, are likely to shed further light on this in coming years.

Signalling pathways in schistosomes: novel targets for control interventions against schistosomiasis

2017 ◽  
Vol 1 (6) ◽  
pp. 633-639 ◽  
Author(s):  
Pengfei Cai ◽  
Donald P. McManus ◽  
Hong You
Keyword(s):  
Functional Characterization ◽  
Cell Signalling ◽  
Signalling Pathways ◽  
Signal Transduction Pathways ◽  
Future Perspectives ◽  
Self Renewal ◽  
Physiological Processes ◽  
Growth Development ◽  
Novel Targets

Over the last decade, there has been accumulating evidence showing that signalling pathways are involved in extensive biological and physiological processes in the human blood fluke schistosomes, playing essential roles in environmental sensing, host penetration, growth, development, maturation, embryogenesis, tissue self-renewal and survival. Owing to the likelihood of resistance developing against praziquantel, the only drug currently available that is effective against all the human schistosome species, there is an urgent requirement for an alternative treatment, arguing for continuing research into novel or repurposed anti-schistosomal drugs. An increasing number of anticancer drugs are being developed which block abnormal signalling pathways, a feature that has stimulated interest in developing novel interventions against human schistosomiasis by targeting key cell signalling components. In this review, we discuss the functional characterization of signal transduction pathways in schistosomes and consider current challenges and future perspectives in this important area of research.

scholarly journals SUMO proteins in the cardiovascular system: friend or foe?

2020 ◽  
Vol 27 (1) ◽  
Author(s):  
Prithviraj Manohar Vijaya Shetty ◽  
Ashraf Yusuf Rangrez ◽  
Norbert Frey
Keyword(s):  
Functional Group ◽  
Current Knowledge ◽  
Signalling Pathways ◽  
Small Peptides ◽  
Post Translational Modifications ◽  
Sumo Modification ◽  
Acetyl Group ◽  
The Impact ◽  
Small Chemical

Abstract Post-translational modifications (PTMs) are crucial for the adaptation of various signalling pathways to ensure cellular homeostasis and proper adaptation to stress. PTM is a covalent addition of a small chemical functional group such as a phosphate group (phosphorylation), methyl group (methylation), or acetyl group (acetylation); lipids like hydrophobic isoprene polymers (isoprenylation); sugars such as a glycosyl group (glycosylation); or even small peptides such as ubiquitin (ubiquitination), SUMO (SUMOylation), NEDD8 (neddylation), etc. SUMO modification changes the function and/or fate of the protein especially under stress conditions, and the consequences of this conjugation can be appreciated from development to diverse disease processes. The impact of SUMOylation in disease has not been monotonous, rather SUMO is found playing a role on both sides of the coin either facilitating or impeding disease progression. Several recent studies have implicated SUMO proteins as key regulators in various cardiovascular disorders. The focus of this review is thus to summarize the current knowledge on the role of the SUMO family in the pathophysiology of cardiovascular diseases.

Emerging Therapeutic Effects of Herbal Plants in Rheumatoid Arthritis

2020 ◽  
Vol 20 ◽  
Author(s):  
Rashita Makkar ◽  
Tapan Behl ◽  
Arun Kumar ◽  
Priya Nijhawan ◽  
Sandeep Arora
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapeutic Potential ◽  
Symptomatic Relief ◽  
Radical Scavenging ◽  
Cartilage Destruction ◽  
Therapeutic Interventions ◽  
Therapeutic Effects ◽  
Cellular Mechanisms ◽  
Current Therapies ◽  
Herbal Plants

Objectives: Rheumatoid arthritis is a chronic inflammatory autoimmune disease characterized by failure of spontaneous resolution of inflammation with lifetime perseverance, becoming one of the major causes of disability in millions of people. It is mainly characterized with progressive erosion of cartilage in response to formation of pannus leading to chronic polyarthritis and joint distortion. Early diagnosis and advances in molecular biology undoubtedly revolutionized therapeutic interventions in the past decade for better disease management. Despite favorable prospects, many patients still fail to respond to the current therapies urging a burning need to develop newer and safer medications. Key findings: Herbal plants have been utilized since ancient era and provided base for massive bioactive compounds with flaunting therapeutic potential, many being advanced to drugs which are consumed worldwide for treating countless ailments. Scientific studies showed involvement of several cellular mechanisms like oxidative stress suppression, downregulated synthesis of proinflammatory cytokines namely interleukins (IL-1, IL-6), TNF-α, NF-κB, demoted metalloproteinases induced cartilage destruction and augmentation of free radical scavenging and antioxidant activity in treatment of rheumatoid arthritis. A plethora of active phytoconstituents like flavonoids, saponins, terpenes, alkaloids, lactones etc have been isolated from herbal plants with proven curative actions. Summary: The present review enlists some of the herbal drugs that can be used to amend the effects of rheumatoid arthritis and impart symptomatic relief to patients.

scholarly journals Dual Role of Chondrocytes in Rheumatoid Arthritis: The Chicken and the Egg

2020 ◽  
Vol 21 (3) ◽  
pp. 1071 ◽  
Author(s):  
Chia-Chun Tseng ◽  
Yi-Jen Chen ◽  
Wei-An Chang ◽  
Wen-Chan Tsai ◽  
Tsan-Teng Ou ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Current Knowledge ◽  
Cartilage Destruction ◽  
Molecular Alterations ◽  
Diagnosis And Prognosis ◽  
Potential Applications ◽  
Biochemical Mechanisms ◽  
Holistic Vision

Rheumatoid arthritis (RA) is one of the inflammatory joint diseases that display features of articular cartilage destruction. The underlying disturbance results from immune dysregulation that directly and indirectly influence chondrocyte physiology. In the last years, significant evidence inferred from studies in vitro and in the animal model offered a more holistic vision of chondrocytes in RA. Chondrocytes, despite being one of injured cells in RA, also undergo molecular alterations to actively participate in inflammation and matrix destruction in the human rheumatoid joint. This review covers current knowledge about the specific cellular and biochemical mechanisms that account for the chondrocyte signatures of RA and its potential applications for diagnosis and prognosis in RA.

Copper as a key regulator of cell signalling pathways

2014 ◽  
Vol 16 ◽  
Author(s):  
Alexandra Grubman ◽  
Anthony R. White
Keyword(s):  
Signal Transduction ◽  
Therapeutic Potential ◽  
Cell Signalling ◽  
Essential Element ◽  
Redox Activity ◽  
Signalling Pathways ◽  
Valuable Insight ◽  
Cellular Mechanisms ◽  
Cell Signal ◽  
Cell Signal Transduction

Copper is an essential element in many biological processes. The critical functions associated with copper have resulted from evolutionary harnessing of its potent redox activity. This same property also places copper in a unique role as a key modulator of cell signal transduction pathways. These pathways are the complex sequence of molecular interactions that drive all cellular mechanisms and are often associated with the interplay of key enzymes including kinases and phosphatases but also including intracellular changes in pools of smaller molecules. A growing body of evidence is beginning to delineate the how, when and where of copper-mediated control over cell signal transduction. This has been driven by research demonstrating critical changes to copper homeostasis in many disorders including cancer and neurodegeneration and therapeutic potential through control of disease-associated cell signalling changes by modulation of copper–protein interactions. This timely review brings together for the first time the diverse actions of copper as a key regulator of cell signalling pathways and discusses the potential strategies for controlling disease-associated signalling processes using copper modulators. It is hoped that this review will provide a valuable insight into copper as a key signal regulator and stimulate further research to promote our understanding of copper in disease and therapy.

Rheumatoid arthritis and dietary interventions: systematic review of clinical trials

2020 ◽  
Author(s):  
Elena Philippou ◽  
Sara Danuta Petersson ◽  
Carrie Rodomar ◽  
Elena Nikiphorou
Keyword(s):  
Rheumatoid Arthritis ◽  
Systematic Review ◽  
Disease Activity ◽  
Current Knowledge ◽  
Data Extraction ◽  
Vitamin D Supplementation ◽  
Dietary Sodium ◽  
Omega 3 ◽  
Dietary Interventions ◽  
The Impact

Abstract Context The impact of various dietary interventions on rheumatoid arthritis (RA), characterized by immune-inflammatory response, has been subject to increased attention. Objective A systematic review was conducted to update the current knowledge on the effects of nutritional, dietary supplement, and fasting interventions on RA outcomes. Data Sources Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with prespecification of all methods, Medline and Embase were systematically searched for relevant articles. Data Extraction Data were extracted by 2 independent reviewers. Results A total of 70 human studies were identified. Administration of omega-3 polyunsaturated fatty acids at high doses resulted in a reduction in RA disease activity and a lower failure rate of pharmacotherapy. Vitamin D supplementation and dietary sodium restriction were beneficial on some RA outcomes. Fasting resulted in significant but transient subjective improvements. While the Mediterranean diet demonstrated improvements in some RA disease activity measures, outcomes from vegetarian, elimination, peptide, or elemental diets suggested that responses are very individualized. Conclusion Some dietary approaches may improve RA symptoms and thus it is recommended that nutrition should be routinely addressed.

scholarly journals Regulation of Annexin I in Rheumatoid Synovial Cells by Glucocorticoids and Interleukin-1

2006 ◽  
Vol 2006 ◽  
pp. 1-6 ◽  
Author(s):  
Eric F. Morand ◽  
Pam Hall ◽  
Paul Hutchinson ◽  
Yuan H. Yang
Keyword(s):  
Rheumatoid Arthritis ◽  
Protein Translocation ◽  
Interleukin 1 ◽  
Signalling Pathways ◽  
Synovial Cells ◽  
Additive Effects ◽  
Intracellular Protein ◽  
Annexin I ◽  
Antiinflammatory Effects ◽  
Fibroblast Like Synoviocytes

The glucocorticoid (GC)-induced antiinflammatory molecule annexin I is expressed in leukocytes and has antiinflammatory effects in animal models of arthritis, but the expression of annexin I in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) is unknown. We report the constitutive and dexamethasone (DEX)-inducible expression of annexin I in RA FLS. DEX increased FLS annexin I protein translocation and mRNA expression. Interleukin (IL)-1βalso induced annexin I translocation and mRNA but also increased intracellular protein. DEX and IL-1 had additive effects on annexin I mRNA, but DEX inhibited the inducing effect of IL-1βon cell surface annexin I. These results indicate that glucocorticoids and IL-1βupregulate the synthesis and translocation of annexin I in RA FLS, but interdependent signalling pathways are involved.

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