scholarly journals Targeting the NLRP3 inflammasome in chronic inflammatory diseases: current perspectives

2015 ◽  
pp. 15 ◽  
Author(s):  
Sarah Doyle ◽  
Ema Ozaki ◽  
Matthew Campbell
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Diseases ◽  
Chronic Inflammatory Diseases

scholarly journals Natural Compounds as Regulators of NLRP3 Inflammasome-Mediated IL-1βProduction

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
József Tőzsér ◽  
Szilvia Benkő
Keyword(s):  
Immune Responses ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Diseases ◽  
Mechanistic Explanation ◽  
Natural Compounds ◽  
The Other ◽  
Oxygen Species ◽  
Molecular Tools ◽  
Chronic Inflammatory Diseases ◽  
Physiological Processes

IL-1βis one of the main proinflammatory cytokines that regulates a broad range of immune responses and also participates in several physiological processes. The canonical production of IL-1βrequires multiprotein complexes called inflammasomes. One of the most intensively studied inflammasome complexes is the NLRP3 inflammasome. Its activation requires two signals: one signal “primes” the cells and induces the expression of NLRP3 and pro-IL-1β, while the other signal leads to the assembly and activation of the complex. Several stimuli were reported to function as the second signal including reactive oxygen species, lysosomal rupture, or cytosolic ion perturbation. Despite very intensive studies, the precise function and regulation of the NLRP3 inflammasome are still not clear. However, many chronic inflammatory diseases are related to the overproduction of IL-1βthat is mediatedviathe NLRP3 inflammasome. In this review, we aimed to provide an overview of studies that demonstrated the effect of plant-derived natural compounds on NLRP3 inflammasome-mediated IL-1βproduction. Although many of these studies lack the mechanistic explanation of their action, these compounds may be considered as complementary supplements in the treatment of chronic inflammatory diseases, consumed as preventive agents, and may also be considered as molecular tools to study NLRP3 function.

scholarly journals Therapeutic regulation of the NLRP3 inflammasome in chronic inflammatory diseases

2021 ◽  
Vol 44 (1) ◽  
pp. 16-35 ◽  
Author(s):  
Jin Kyung Seok ◽  
Han Chang Kang ◽  
Yong-Yeon Cho ◽  
Hye Suk Lee ◽  
Joo Young Lee
Keyword(s):  
Pattern Recognition ◽  
Small Molecule ◽  
Nlrp3 Inflammasome ◽  
Small Molecule Inhibitors ◽  
Inflammatory Diseases ◽  
Cellular Damage ◽  
Receptor Protein ◽  
Current Status ◽  
Chronic Inflammatory Diseases ◽  
Molecular Patterns

AbstractInflammasomes are cytosolic pattern recognition receptors that recognize pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) derived from invading pathogens and damaged tissues, respectively. Upon activation, the inflammasome forms a complex containing a receptor protein, an adaptor, and an effector to induce the autocleavage and activation of procaspase-1 ultimately culminating in the maturation and secretion of IL-1β and IL-18 and pyroptosis. Inflammasome activation plays an important role in host immune responses to pathogen infections and tissue repair in response to cellular damage. The NLRP3 inflammasome is a well-characterized pattern recognition receptor and is well known for its critical role in the regulation of immunity and the development and progression of various inflammatory diseases. In this review, we summarize recent efforts to develop therapeutic applications targeting the NLRP3 inflammasome to cure and prevent chronic inflammatory diseases. This review extensively discusses NLRP3 inflammasome-related diseases and current development of small molecule inhibitors providing beneficial information on the design of therapeutic strategies for NLRP3 inflammasome-related diseases. Additionally, small molecule inhibitors are classified depending on direct or indirect targeting mechanism to describe the current status of the development of pharmacological inhibitors.

scholarly journals Structural Moieties Required for Cinnamaldehyde-Related Compounds to Inhibit Canonical IL-1β Secretion

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3241 ◽  
Author(s):  
Su-Chen Ho ◽  
Yi-Huang Chang ◽  
Ku-Shang Chang
Keyword(s):  
Nlrp3 Inflammasome ◽  
Functional Group ◽  
Inflammatory Diseases ◽  
Receptor Protein ◽  
Side Chain ◽  
Activated Macrophages ◽  
Inhibitory Effects ◽  
Chronic Inflammatory Diseases ◽  
Caspase 1 ◽  
Related Compounds

Suppressing canonical NOD-like receptor protein 3 (NLRP3) inflammasome-mediated interleukin (IL)-1β secretion is a reliable strategy for the development of nutraceutical to prevent chronic inflammatory diseases. This study aimed to find out the functional group responsible for the inhibitory effects of cinnamaldehyde-related compounds on the canonical IL-1β secretion. To address this, the suppressing capacities of six cinnamaldehyde-related compounds were evaluated and compared by using the lipopolysaccharide (LPS)-primed and adenosine 5′-triphosphate (ATP)-activated macrophages. At concentrations of 25~100 μM, cinnamaldehyde and 2-methoxy cinnamaldehyde dose-dependently inhibited IL-1β secretion. In contrast, cinnamic acid, cinnamyl acetate, cinnamyl alcohol and α-methyl cinnamaldehyde did not exert any inhibition. Furthermore, cinnamaldehyde and 2-methoxy cinnamaldehyde diminished expressions of NLRP3 and pro-IL-1β. Meanwhile, cinnamaldehyde and 2-methoxy cinnamaldehyde prevented the ATP-induced reduction of cytosolic pro-caspase-1 and increase of secreted caspase-1. In conclusion, for cinnamaldehyde-related compounds to suppress NLRP3 inflammasome-mediated IL-1β secretion, the propenal group of the side chain was essential, while the substituted group of the aromatic ring played a modifying role. Cinnamaldehyde and 2-methoxy cinnamaldehyde exerted dual abilities to inhibit canonical IL-1β secretion at both stages of priming and activation. Therefore, there might be potential to serve as complementary supplements for the prevention of chronic inflammatory diseases.

Chronic Inflammatory Diseases: Progress and Prospect with Herbal Medicine

2015 ◽  
Vol 22 (2) ◽  
pp. 247-264 ◽  
Author(s):  
Nilanjan Ghosh ◽  
Asif Ali ◽  
Rituparna Ghosh ◽  
Shaileyee Das ◽  
Subhash C. Mandal ◽  
...  
Keyword(s):  
Herbal Medicine ◽  
Inflammatory Diseases ◽  
Chronic Inflammatory Diseases

Exploiting Anti-Inflammation Effects of Flavonoids in Chronic Inflammatory Diseases

2020 ◽  
Vol 26 (22) ◽  
pp. 2610-2619 ◽  
Author(s):  
Tarique Hussain ◽  
Ghulam Murtaza ◽  
Huansheng Yang ◽  
Muhammad S. Kalhoro ◽  
Dildar H. Kalhoro
Keyword(s):  
Oxidative Stress ◽  
Chronic Diseases ◽  
Inflammatory Diseases ◽  
Therapeutic Option ◽  
Cellular Level ◽  
Antiinflammatory Drugs ◽  
Suitable Alternative ◽  
Chronic Inflammatory Diseases

Background: Inflammation is a complex response of the host defense system to different internal and external stimuli. It is believed that persistent inflammation may lead to chronic inflammatory diseases such as, inflammatory bowel disease, neurological and cardiovascular diseases. Oxidative stress is the main factor responsible for the augmentation of inflammation via various molecular pathways. Therefore, alleviating oxidative stress is effective a therapeutic option against chronic inflammatory diseases. Methods: This review article extends the knowledge of the regulatory mechanisms of flavonoids targeting inflammatory pathways in chronic diseases, which would be the best approach for the development of suitable therapeutic agents against chronic diseases. Results: Since the inflammatory response is initiated by numerous signaling molecules like NF-κB, MAPK, and Arachidonic acid pathways, their encountering function can be evaluated with the activation of Nrf2 pathway, a promising approach to inhibit/prevent chronic inflammatory diseases by flavonoids. Over the last few decades, flavonoids drew much attention as a potent alternative therapeutic agent. Recent clinical evidence has shown significant impacts of flavonoids on chronic diseases in different in-vivo and in-vitro models. Conclusion: Flavonoid compounds can interact with chronic inflammatory diseases at the cellular level and modulate the response of protein pathways. A promising approach is needed to overlook suitable alternative compounds providing more therapeutic efficacy and exerting fewer side effects than commercially available antiinflammatory drugs.

scholarly journals Lipid, fatty acid, carnitine- and choline derivative profiles in rheumatoid arthritis outpatients with different degrees of periodontal inflammation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kathrin Beyer ◽  
Stein Atle Lie ◽  
Bodil Bjørndal ◽  
Rolf K. Berge ◽  
Asbjørn Svardal ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Fatty Acid ◽  
Mitochondrial Dysfunction ◽  
Inflammatory Diseases ◽  
Whole Body ◽  
Cross Sectional ◽  
Chronic Inflammatory Diseases ◽  
Periodontal Inflammation ◽  
Inflammatory Status ◽  
Lipid Fatty Acid

AbstractRheumatoid arthritis (RA) and periodontitis are chronic inflammatory diseases with several pathogenic pathways in common. Evidence supports an association between the diseases, but the exact underlying mechanisms behind the connection are still under investigation. Lipid, fatty acid (FA) and metabolic profile alterations have been associated with several chronic inflammatory diseases, including RA and periodontitis. Mitochondria have a central role in regulating cellular bioenergetic and whole-body metabolic homeostasis, and mitochondrial dysfunction has been proposed as a possible link between the two disorders. The aim of this cross-sectional study was to explore whole-blood FA, serum lipid composition, and carnitine- and choline derivatives in 78 RA outpatients with different degrees of periodontal inflammation. The main findings were alterations in lipid, FA, and carnitine- and choline derivative profiles. More specifically, higher total FA and total cholesterol concentrations were found in active RA. Elevated phospholipid concentrations with concomitant lower choline, elevated medium-chain acylcarnitines (MC-AC), and decreased ratios of MC-AC and long-chain (LC)-AC were associated with prednisolone medication. This may indicate an altered mitochondrial function in relation to the increased inflammatory status in RA disease. Our findings may support the need for interdisciplinary collaboration within the field of medicine and dentistry in patient stratification to improve personalized treatment. Longitudinal studies should be conducted to further assess the potential impact of mitochondrial dysfunction on RA and periodontitis.

scholarly journals Techniques to Study Inflammasome Activation and Inhibition by Small Molecules

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1704
Author(s):  
Diego Angosto-Bazarra ◽  
Cristina Molina-López ◽  
Alejandro Peñín-Franch ◽  
Laura Hurtado-Navarro ◽  
Pablo Pelegrín
Keyword(s):  
Inflammatory Response ◽  
Small Molecules ◽  
Mechanism Of Action ◽  
Inflammatory Diseases ◽  
Inflammasome Activation ◽  
Chronic Inflammatory Diseases ◽  
Anti Inflammatory ◽  
Inhibitory Molecules ◽  
Inflammasome Inhibitors

Inflammasomes are immune cytosolic oligomers involved in the initiation and progression of multiple pathologies and diseases. The tight regulation of these immune sensors is necessary to control an optimal inflammatory response and recover organism homeostasis. Prolonged activation of inflammasomes result in the development of chronic inflammatory diseases, and the use of small drug-like inhibitory molecules are emerging as promising anti-inflammatory therapies. Different aspects have to be taken in consideration when designing inflammasome inhibitors. This review summarizes the different techniques that can be used to study the mechanism of action of potential inflammasome inhibitory molecules.

scholarly journals Impact of COVID-19 on initiation of biologic therapy prescriptions for chronic inflammatory diseases

2021 ◽  
pp. 105253
Author(s):  
Pascal Richette ◽  
Matthieu Allez ◽  
Vincent Descamps ◽  
Lucas Perray ◽  
Simon Pilet ◽  
...  
Keyword(s):  
Biologic Therapy ◽  
Inflammatory Diseases ◽  
Chronic Inflammatory Diseases

scholarly journals The mercapturomic profile of health and non-communicable diseases

2019 ◽  
Vol 8 (2) ◽  
pp. 10 ◽  
Author(s):  
Gonçalves-Dias ◽  
Morello ◽  
Semedo ◽  
Correia ◽  
Coelho ◽  
...  
Keyword(s):  
Environmental Exposure ◽  
Inflammatory Diseases ◽  
Communicable Diseases ◽  
Non Communicable Diseases ◽  
Chronic Inflammatory Diseases ◽  
Cardiometabolic Diseases ◽  
Health And Disease ◽  
Endogenous Metabolites

The mercapturate pathway is a unique metabolic circuitry that detoxifies electrophiles upon adducts formation with glutathione. Since its discovery over a century ago, most of the knowledge on the mercapturate pathway has been provided from biomonitoring studies on environmental exposure to toxicants. However, the mercapturate pathway-related metabolites that is formed in humans—the mercapturomic profile—in health and disease is yet to be established. In this paper, we put forward the hypothesis that these metabolites are key pathophysiologic factors behind the onset and development of non-communicable chronic inflammatory diseases. This review goes from the evidence in the formation of endogenous metabolites undergoing the mercapturate pathway to the methodologies for their assessment and their association with cancer and respiratory, neurologic and cardiometabolic diseases.

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