scholarly journals Alarmins in Osteoporosis, RAGE, IL-1, and IL-33 Pathways: A Literature Review

Medicina ◽  
2020 ◽  
Vol 56 (3) ◽  
pp. 138 ◽  
Author(s):  
Massimo De Martinis ◽  
Lia Ginaldi ◽  
Maria Maddalena Sirufo ◽  
Giovanni Pioggia ◽  
Gioacchino Calapai ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
High Mobility ◽  
Fragility Fractures ◽  
Signal Pathways ◽  
Type I ◽  
Scientific Databases ◽  
Physiological Processes ◽  
Pharmacological Targets ◽  
Bibliographic Search

Alarmins are endogenous mediators released by cells following insults or cell death to alert the host’s innate immune system of a situation of danger or harm. Many of these, such as high-mobility group box-1 and 2 (HMGB1, HMGB2) and S100 (calgranulin proteins), act through RAGE (receptor for advanced glycation end products), whereas the IL-1 and IL-33 cytokines bind the IL-1 receptors type I and II, and the cellular receptor ST2, respectively. The alarmin family and their signal pathways share many similarities of cellular and tissue localization, functions, and involvement in various physiological processes and inflammatory diseases including osteoporosis. The aim of the review was to evaluate the role of alarmins in osteoporosis. A bibliographic search of the published scientific literature regarding the role of alarmins in osteoporosis was organized independently by two researchers in the following scientific databases: Pubmed, Scopus, and Web of Science. The keywords used were combined as follows: “alarmins and osteoporosis”, “RAGE and osteoporosis”, “HMGB1 and osteoporosis”, “IL-1 and osteoporosis”, “IL 33 and osteopororsis”, “S100s protein and osteoporosis”. The information was summarized and organized in the present review. We highlight the emerging roles of alarmins in various bone remodeling processes involved in the onset and development of osteoporosis, as well as their potential role as biomarkers of osteoporosis severity and progression. Findings of the research suggest a potential use of alarmins as pharmacological targets in future therapeutic strategies aimed at preventing bone loss and fragility fractures induced by aging and inflammatory diseases.

scholarly journals Selective Tyrosine Kinase 2 Inhibition for Treatment of Inflammatory Bowel Disease: New Hope on the Rise

2021 ◽  
Author(s):  
Silvio Danese ◽  
Laurent Peyrin-Biroulet
Keyword(s):  
Inflammatory Bowel Disease ◽  
Tyrosine Kinase ◽  
Bowel Disease ◽  
Inflammatory Diseases ◽  
Janus Kinase ◽  
Type I ◽  
Tyrosine Kinase 2 ◽  
Immune Mediated ◽  
Inflammatory Bowel

Abstract Conventional systemic and biologic agents are the mainstay of inflammatory bowel disease (IBD) management; however, many of these agents are associated with loss of clinical response, highlighting the need for effective, novel targeted therapies. Janus kinase (JAK) 1-3 and tyrosine kinase 2 (TYK2) mediate signal transduction events downstream of multiple cytokine receptors that regulate targeted gene transcription, including the interleukin-12, interleukin-23, and type I interferon receptors for TYK2. This review summarizes the role of TYK2 signaling in IBD pathogenesis, the differential selectivity of TYK2 inhibitors, and the potential clinical implications of TYK2 inhibition in IBD. A PubMed literature review was conducted to identify studies of JAK1-3 and TYK2 inhibitors in IBD and other immune-mediated inflammatory diseases. Key efficacy and safety information was extracted and summarized. Pan-JAK inhibitors provide inconsistent efficacy in patients with IBD and are associated with toxicities resulting from a lack of selectivity at therapeutic dosages. Selective inhibition of TYK2 signaling via an allosteric mechanism, with an agent that binds to the regulatory (pseudokinase) domain, may reduce potential toxicities typically associated with JAK1-3 inhibitors. Deucravacitinib, a novel, oral, selective TYK2 inhibitor, and brepocitinib and PF-06826647, TYK2 inhibitors that bind to the active site in the catalytic domain, are in development for IBD and other immune-mediated inflammatory diseases. Allosteric TYK2 inhibition is more selective than JAK1-3 inhibition and has the potential to limit toxicities typically associated with JAK1-3 inhibitors. Future studies will be important in establishing the role of selective, allosteric TYK2 inhibition in the management of IBD.

scholarly journals The Role of HDAC6 in Autophagy and NLRP3 Inflammasome

2021 ◽  
Vol 12 ◽  
Author(s):  
Panpan Chang ◽  
Hao Li ◽  
Hui Hu ◽  
Yongqing Li ◽  
Tianbing Wang
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Histone Deacetylase 6 ◽  
Physiological Processes ◽  
Class Iib ◽  
Underlying Mechanisms ◽  
Nlrp3 Inflammasomes ◽  
Insight Into

Autophagy fights against harmful stimuli and degrades cytosolic macromolecules, organelles, and intracellular pathogens. Autophagy dysfunction is associated with many diseases, including infectious and inflammatory diseases. Recent studies have identified the critical role of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasomes activation in the innate immune system, which mediates the secretion of proinflammatory cytokines IL-1β/IL-18 and cleaves Gasdermin D to induce pyroptosis in response to pathogenic and sterile stimuli. Accumulating evidence has highlighted the crosstalk between autophagy and NLRP3 inflammasome in multifaceted ways to influence host defense and inflammation. However, the underlying mechanisms require further clarification. Histone deacetylase 6 (HDAC6) is a class IIb deacetylase among the 18 mammalian HDACs, which mainly localizes in the cytoplasm. It is involved in two functional deacetylase domains and a ubiquitin-binding zinc finger domain (ZnF-BUZ). Due to its unique structure, HDAC6 regulates various physiological processes, including autophagy and NLRP3 inflammasome, and may play a role in the crosstalk between them. In this review, we provide insight into the mechanisms by which HDAC6 regulates autophagy and NLRP3 inflammasome and we explored the possibility and challenges of HDAC6 in the crosstalk between autophagy and NLRP3 inflammasome. Finally, we discuss HDAC6 inhibitors as a potential therapeutic approach targeting either autophagy or NLRP3 inflammasome as an anti-inflammatory strategy, although further clarification is required regarding their crosstalk.

scholarly journals Histamine and its Effects Mediated via H3 Receptor – Potential Clinical Applications of H3 Antagonists

2013 ◽  
Vol 13 (Supplement-1) ◽  
pp. 28-36
Author(s):  
E. Hanuskova ◽  
J. Plevkova
Keyword(s):  
First Generation ◽  
Inflammatory Diseases ◽  
Receptor Potential ◽  
Allergic Diseases ◽  
Histamine Receptor ◽  
Clinical Applications ◽  
Receptor Antagonists ◽  
Physiological Processes ◽  
Inflammatory Drugs

Abstract Histamine is one of the most important biogenic amines and it mediates numbers of physiological processes. It is also involved in majority of inflammatory diseases via its receptors H1, H2, H3 and H4. The role of histamine had been recognized as substantial in many allergic diseases including bronchial asthma, thus the histamine receptor antagonists (H1) are frequently used in the clinical practice as potent anti-allergic and anti-inflammatory drugs. However, first generation of antihistamines have also adverse effects, predominantly sedation, changes in appetite and many more, and they are still not fully effective in all patients. Attention is now focused mainly on H3 and H4 receptor antagonists and their potential clinical applications. This review focuses basically on the H3 receptor, its expression pattern and some effects which are mediated by H3, discussing its clinical relevance

An overview of high-mobility group box 1, a potent pro-inflammatory cytokine in asthma

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Farzaneh Kianian ◽  
Mehri Kadkhodaee ◽  
Hamid Reza Sadeghipour ◽  
Seyed Morteza Karimian ◽  
Behjat Seifi
Keyword(s):  
Inflammatory Cytokine ◽  
Inflammatory Diseases ◽  
High Mobility ◽  
Chronic Respiratory Disease ◽  
High Mobility Group ◽  
High Morbidity ◽  
Surface Receptors ◽  
Nucleosome Formation ◽  
Central Characteristic

AbstractHigh-mobility group box 1 (HMGB1), also called amphoterin, HMG1 and p30, is a highly conserved protein between different species that has various functions in nucleus such as stabilization of nucleosome formation, facilitation of deoxyribonucleic acid (DNA) bending and increasing the DNA transcription, replication and repair. It has also been indicated that HMGB1 acts as a potent pro-inflammatory cytokine with increasing concentrations in acute and chronic inflammatory diseases. Asthma is a common chronic respiratory disease associated with high morbidity and mortality rates. One central characteristic in its pathogenesis is airway inflammation. Considering the inflammatory role of HMGB1 and importance of inflammation in asthma pathogenesis, a better understanding of this protein is vital. This review describes the structure, cell surface receptors, signaling pathways and intracellular and extracellular functions of HMGB1, but also focuses on its inflammatory role in asthma. Moreover, this manuscript reviews experimental and clinical studies that investigated the pathologic role of HMGB1.

scholarly journals Remarkable Role of Indoleamine 2,3-Dioxygenase and Tryptophan Metabolites in Infectious Diseases: Potential Role in Macrophage-Mediated Inflammatory Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Yuki Murakami ◽  
Masato Hoshi ◽  
Yukio Imamura ◽  
Yuko Arioka ◽  
Yasuko Yamamoto ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Therapeutic Strategies ◽  
Type I Interferons ◽  
Regulatory Function ◽  
Type I ◽  
Indoleamine 2,3 Dioxygenase ◽  
Tryptophan Metabolites

Indoleamine 2,3-dioxygenase 1 (IDO1), the L-tryptophan-degrading enzyme, plays a key role in the immunomodulatory effects on several types of immune cells. Originally known for its regulatory function during pregnancy and chronic inflammation in tumorigenesis, the activity of IDO1 seems to modify the inflammatory state of infectious diseases. The pathophysiologic activity of L-tryptophan metabolites, kynurenines, is well recognized. Therefore, an understanding of the regulation of IDO1 and the subsequent biochemical reactions is essential for the design of therapeutic strategies in certain immune diseases. In this paper, current knowledge about the role of IDO1 and its metabolites during various infectious diseases is presented. Particularly, the regulation of type I interferons (IFNs) production via IDO1 in virus infection is discussed. This paper offers insights into new therapeutic strategies in the modulation of viral infection and several immune-related disorders.

scholarly journals Role of microRNAs in the process of metformin treating multiple diseases

2021 ◽  
Vol 1 (2) ◽  
pp. 69-78
Author(s):  
Ningning Ma ◽  
Jing Chen ◽  
Jin Ren
Keyword(s):  
Metabolic Diseases ◽  
Expression Profiles ◽  
Signal Pathways ◽  
Beneficial Effects ◽  
New Class ◽  
Disease States ◽  
Physiological Processes ◽  
Pleiotropic Properties

Abstract Metformin as the first-line treatment for type 2 diabetes mellitus has been discovered to exert beneficial effects on many diseases for nearly ten years, but its specific mechanism is still unclear. As a new class of gene expression regulators with pleiotropic properties, microRNAs (miRNAs) participate in multiple physiological processes such as cell differentiation, proliferation, survival, and metabolism, which drive them to play a regulatory role in the occurrence, development and even treatment of various diseases. A substantial body of research has found the relationship between metformin and miRNAs, in which metformin can alter the expression profiles of miRNAs in multiple disease states and on the other hand the signal pathways involving miRNAs may contribute to the pharmacological actions of metformin. This review summarizes the effects of metformin on miRNAs and their relationship in different diseases (like tumor, metabolic diseases, etc.), which should be of a great help for our better understanding of the mechanism of metformin for treating multiple diseases.

scholarly journals HMGB1 Aggravates Pressure Overload-Induced Left Ventricular Dysfunction by Promoting Myocardial Fibrosis

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Lei Zhang ◽  
Ying Yu ◽  
Peng Yu ◽  
Jian Wu ◽  
Aijun Sun ◽  
...  
Keyword(s):  
Cardiac Fibrosis ◽  
Collagen Type ◽  
Cardiac Injury ◽  
Pressure Overload ◽  
High Mobility ◽  
Collagen Type I ◽  
Left Ventricular ◽  
Type I ◽  
Lv Dysfunction

Aim. Fibrosis had important effects on pressure overload-induced left ventricular (LV) dysfunction. High-mobility group box 1 (HMGB1), which was closely associated with fibrosis, was involved in the pressure overload-induced cardiac injury. This study determines the role of HMGB1 in LV dysfunction under pressure overload. Methods. Transverse aortic constriction (TAC) operation was performed on male C57BL/6J mice to build the model of pressure overload, while HMGB1 or PBS was injected into the LV wall. Cardiac function, collagen volume, and relevant genes were detected. Results. Echocardiography demonstrated that the levels of LV ejection fraction (LVEF) were markedly decreased on day 28 after TAC, which was consistent with raised collagen in the myocardium. Moreover, we found that the exposure of mice to TAC + HMGB1 is associated with higher mortality, BNP, and collagen volume in the myocardium and lower LVEF. In addition, real-time PCR showed that the expression of collagen type I, TGF-β, and MMP2 markedly increased in the myocardium after TAC, while HMGB1 overexpression further raised the TGF-β expression but not collagen type I and MMP2 expressions. Conclusion. This study indicated that exogenous HMGB1 overexpression in the myocardium aggravated the pressure overload-induced LV dysfunction by promoting cardiac fibrosis, which may be mediated by increasing the TGF-β expression.

Mast Cells as a Double Edged Sword in Immunity: Disorders of Mast Cell Activation and Therapeutic Management. Second of Two Parts

2020 ◽  
Vol 20 (5) ◽  
pp. 670-686 ◽  
Author(s):  
Thea Magrone ◽  
Manrico Magrone ◽  
Emilio Jirillo
Keyword(s):  
Mast Cells ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Allergen Immunotherapy ◽  
Inflammatory Diseases ◽  
Protective Role ◽  
Mast Cell Activation ◽  
Parasitic Infections ◽  
Type I

: Mast cells (MCs) bear many receptors which allow them to respond tAs far as treatment of MC-derived diseases is concerned, allergen immunotherapy as well as other attempts to reduce MC-activation will be outlined according to the recent data. Finally, in agreement with current literature and our own data polyphenols have been demonstrated to attenuate type I allergic reactions and contact dermatitis in response to nickel. The use of polyphenols in these diseases will be discussed also in view of MC involvement.o a variety of exogenous and endogenous stimuli. However, MC function is dual since they can initiate pathological events or protect the host against infectious challenges. : The role of MCs in disease will be analyzed in a broad sense, describing cellular and molecular mechanisms related to their involvement in auto-inflammatory diseases, asthma, autoimmune diseases and cancer. On the other hand, their protective role in the course of bacterial, fungal and parasitic infections will also be illustrated. : Mast cells (MCs) bear many receptors that allow them to respond to a variety of exogenous and endogenous stimuli. However, MC function is dual since they can initiate pathological events or protect the host against infectious challenges.

scholarly journals The Role of Metal Regulatory Proteins in Brain Oxidative Stress: A Tutorial

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Wayne Briner
Keyword(s):  
Oxidative Stress ◽  
Redox Activity ◽  
Biological Processes ◽  
Physiological Processes ◽  
Pharmacological Targets ◽  
Wide Range ◽  
Brain Oxidative Stress ◽  
The Brain ◽  
And Oxidative Stress

The proteins that regulate the metabolism of a metal must also play a role in regulating the redox activity of the metal. Metals are intrinsic to a substantial number of biological processes and the proteins that regulate those activities are also considerable in number. The role these proteins play in a wide range of physiological processes involves them directly and indirectly in a variety of disease processes. Similarly, it may be therapeutically advantageous to pharmacologically alter the activity of these metal containing proteins to influence disease processes. This paper will introduce the reader to a number of important proteins in both metal metabolism and oxidative stress, with an emphasis on the brain. Potential pharmacological targets will be considered.

scholarly journals Tumorigenic Aspects of MSC Senescence—Implication in Cancer Development and Therapy

2021 ◽  
Vol 11 (11) ◽  
pp. 1133
Author(s):  
Slavko Mojsilović ◽  
Aleksandra Jauković ◽  
Tamara Kukolj ◽  
Hristina Obradović ◽  
Ivana Okić Đorđević ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Tumor Development ◽  
The Elderly ◽  
Low Grade ◽  
Innate And Adaptive Immunity ◽  
Physiological Processes ◽  
Age Related ◽  
Tumor Prevention ◽  
Stromal Stem Cells

As an organism ages, many physiological processes change, including the immune system. This process, called immunosenescence, characterized by abnormal activation and imbalance of innate and adaptive immunity, leads to a state of chronic low-grade systemic inflammation, termed inflammaging. Aging and inflammaging are considered to be the root of many diseases of the elderly, as infections, autoimmune and chronic inflammatory diseases, degenerative diseases, and cancer. The role of mesenchymal stromal/stem cells (MSCs) in the inflammaging process and the age-related diseases is not completely established, although numerous features of aging MSCs, including altered immunomodulatory properties, impeded MSC niche supporting functions, and senescent MSC secretory repertoire are consistent with inflammaging development. Although senescence has its physiological function and can represent a mechanism of tumor prevention, in most cases it eventually transforms into a deleterious (para-)inflammatory process that promotes tumor growth. In this review we are going through current literature, trying to explore the role of senescent MSCs in making and/or sustaining a microenvironment permissive to tumor development and to analyze the therapeutic options that could target this process.

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