Summary
Inflammatory responses mediated by macrophages are part of the innate immune system, whose role is to protect against invading pathogens. Lipopolysaccharide (LPS) found in the outer membrane ...of Gram‐negative bacteria stimulates an inflammatory response by macrophages. During the inflammatory response, extracellular LPS is recognized by Toll‐like receptor 4, one of the pattern recognition receptors that activates inflammatory signalling pathways and leads to the production of inflammatory mediators. The innate immune response is also triggered by intracellular inflammasomes, and inflammasome activation induces pyroptosis and the secretion of pro‐inflammatory cytokines such as interleukin‐1β (IL‐1β) and IL‐18 by macrophages. Cysteine‐aspartic protease (caspase)‐11 and the human orthologues caspase‐4/caspase‐5 were recently identified as components of the ‘non‐canonical inflammasome’ that senses intracellular LPS derived from Gram‐negative bacteria during macrophage‐mediated inflammatory responses. Direct recognition of intracellular LPS facilitates the rapid oligomerization of caspase‐11/4/5, which results in pyroptosis and the secretion of IL‐1β and IL‐18. LPS is released into the cytoplasm from Gram‐negative bacterium‐containing vacuoles by small interferon‐inducible guanylate‐binding proteins encoded on chromosome 3 (GBPchr3)‐mediated lysis of the vacuoles. In vivo studies have clearly shown that caspase‐11−/− mice are more resistant to endotoxic septic shock by excessive LPS challenge. Given the evidence, activation of caspase‐11 non‐canonical inflammasomes by intracellular LPS is distinct from canonical inflammasome activation and provides a new paradigm in macrophage‐mediated inflammatory responses.
Caspase‐11 non‐canonical inflammasome recognizes intracellular lipopolysaccharide and activates caspase‐1, resulting in pyroptosis and secretion of interleukin‐1β and interleukin‐18 in macrophages during inflammatory responses.
Inflammation is an innate immune response to noxious stimuli to protect the body from pathogens. Inflammatory responses consist of two main steps: priming and triggering. In priming, inflammatory ...cells increase expressions of inflammatory molecules, while in triggering, inflammasomes are activated, resulting in cell death and pro‐inflammatory cytokine secretion. Inflammasomes are protein complexes comprising intracellular pattern recognition receptors (PRRs) (e.g., nucleotide‐binding oligomerization domain‐like receptors (NLRs), absent in melanoma 2 (AIM2), and caspases‐4/5/11) and pro‐caspase‐1 with or without a bipartite adaptor molecule ASC. Inflammasome activation induces pyroptosis, inflammatory cell death, and stimulates caspase‐1‐mediated secretion of interleukin (IL)‐1b and IL‐18. Flavonoids are secondary metabolites found in various plants and are considered as critical ingredients promoting health and ameliorating various disease symptoms. Anti‐inflammatory activity of flavonoids and underlying mechanisms have been widely studied. This review introduces current knowledge on different types of inflammasomes and their activation during inflammatory responses and discusses recent studies regarding anti‐inflammatory roles of flavonoids as suppressors of inflammasomes in inflammatory conditions. Understanding the regulatory effects of flavonoids on inflammasome activation will increase our knowledge of flavonoid‐mediated anti‐inflammatory activity and provide new insights into the development of flavonoid preparations to prevent and treat human inflammatory diseases.
An up‐to‐date review on the anti‐inflammatory activity of flavonoids, including quercetin, luteolin, apigenin, epigallocatechin gallate (EGCG), rutin, isoliquiritigenin (ISL), and procyanidins, focusing on the inhibition of inflammasome activation in inflamed cells, is given. Flavonoids play a suppressive role on inflammatory responses and the pathogenesis of inflammatory diseases by inhibiting the activation of various types of inflammasomes, such as NLRP1, NLRP3, NLRC4, and AIM2 inflammasomes in inflamed cells. The anti‐inflammatory property of flavonoids by inhibiting inflammasome activation, a critical mechanism to suppress inflammatory responses, and flavonoid‐mediated selective targeting of inflammasome components could be a promising strategy to prevent and treat inflammatory diseases.
Summary
Inflammation is a part of the body's immune response for protection against pathogenic infections and other cellular damages; however, chronic inflammation is a major cause of various ...diseases. One key step in the inflammatory response is the activation of inflammasomes, intracellular protein complexes comprising pattern recognition receptors and other inflammatory molecules. The role of the NLRP3 inflammasome in inflammatory responses has been extensively investigated; however, the caspase‐11 inflammasome has been recently identified and has been classified as a ‘non‐canonical’ inflammasome, and emerging studies have highlighted its role in inflammatory responses. Because the ligands and the mechanisms for the activation of these two inflammasomes are different, studies to date have separately described their roles, although recent studies have reported the functional cooperation between these two inflammasomes during an inflammatory response. This review discusses the studies investigating the functional crosstalk between non‐canonical caspase‐11 and canonical NLRP3 inflammasomes in the context of inflammatory responses; moreover, it provides insight for the development of novel anti‐inflammatory therapeutics to prevent and treat infectious and inflammatory diseases.
The functional crosstalk between the non‐canonical caspase‐11 inflammasome and the canonical NLRP3 inflammasome, the most extensively studied canonical inflammasome during inflammatory responses and the pathogenesis of infectious and inflammatory diseases.
Ginseng is an ethnopharmacological herbal plant in Asian countries, particularly in Korea, China, and Japan. Ginseng saponins, including ginsenosides, are major active components in ginseng and have ...been demonstrated to have numerous pharmacological effects on various human diseases.
Many previous studies investigating the anti-inflammatory effect of ginseng saponins have mostly focused on the ‘priming’ step rather than the ‘triggering’ step. This review aims to discuss the studies investigating an inhibitory role of ginseng saponins in inflammasome activation of the triggering step.
The literature was explored using the search strings, such as “ginseng saponins and inflammasomes” and “ginsenosides and inflammasomes” in several resources, such as PubMed, Google Scholar, and Scopus databases.
Various ginseng saponins of Panax ginseng, Panax japonicas, and Panax quinquefolius alleviated inflammatory responses and diseases by inhibiting the nucleotide-binding oligomerization domain-like receptor (NLR) P3 (NLRP3) inflammasome activation. Also, ginseng saponin, Rg1 of Panax ginseng alleviated neuroinflammation and diseases by inhibiting NLRP1 inflammasome activation. Finally, ginseng saponins, Rh1 and Rg3 in Korea red ginseng (KRG) of Panax ginseng ameliorated sepsis by inhibiting absent in melanoma 2 (AIM2) inflammasome activation.
The studies discussed in this review provide insight into the new paradigm of the ginseng saponins as the promising anti-inflammatory agents that could be ethnopharmacologically used to prevent and treat inflammatory and inflammation-induced disorders via targeting inflammasomes.
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Inflammation is a body's protective mechanism to eliminate invading pathogens and cellular damaging signals. The inflammatory response consists of two main consecutive steps-a priming step preparing ...the inflammatory responses and a triggering step boosting the inflammatory responses. The main feature of the triggering step is the activation of the inflammasome, an intracellular multiprotein complex facilitating the inflammatory responses. The regulatory roles of 'canonical' inflammasomes in the inflammatory responses and diseases have been largely investigated, so far. New types of inflammasomes have been recently discovered and named as 'non-canonical' inflammasomes since their roles to induce inflammatory responses are similar to those of canonical inflammasomes, however, the stimulating ligands and the underlying mechanisms are different. Therefore, a growing number of studies have actively investigated the novel roles of non-canonical inflammasomes in inflammatory responses and diseases. This review summarizes and discusses the recent studies exploring the regulatory roles of caspase-11 non-canonical inflammasome during the inflammatory responses and provides insight into the development of novel therapeutics for infectious and inflammatory diseases by targeting caspase-11 non-canonical inflammasome.
Inflammasomes are multiprotein complexes that activate inflammatory responses by inducing pyroptosis and secretion of pro-inflammatory cytokines. Along with many previous studies on inflammatory ...responses and diseases induced by canonical inflammasomes, an increasing number of studies have demonstrated that non-canonical inflammasomes, such as mouse caspase-11 and human caspase-4 inflammasomes, are emerging key players in inflammatory responses and various diseases. Flavonoids are natural bioactive compounds found in plants, fruits, vegetables, and teas and have pharmacological properties in a wide range of human diseases. Many studies have successfully demonstrated that flavonoids play an anti-inflammatory role and ameliorate many inflammatory diseases by inhibiting canonical inflammasomes. Others have demonstrated the anti-inflammatory roles of flavonoids in inflammatory responses and various diseases, with a new mechanism by which flavonoids inhibit non-canonical inflammasomes. This review discusses recent studies that have investigated the anti-inflammatory roles and pharmacological properties of flavonoids in inflammatory responses and diseases induced by non-canonical inflammasomes and further provides insight into developing flavonoid-based therapeutics as potential nutraceuticals against human inflammatory diseases.
Inflammasomes are intracellular multiprotein complexes that activate inflammatory signaling pathways. Inflammasomes comprise two major classes: canonical inflammasomes, which were discovered first ...and are activated in response to a variety of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs), and non-canonical inflammasomes, which were discovered recently and are only activated in response to intracellular lipopolysaccharide (LPS). Although a larger number of studies have successfully demonstrated that canonical inflammasomes, particularly the NLRP3 inflammasome, play roles in various rheumatic diseases, including rheumatoid arthritis (RA), infectious arthritis (IR), gouty arthritis (GA), osteoarthritis (OA), systemic lupus erythematosus (SLE), psoriatic arthritis (PA), ankylosing spondylitis (AS), and Sjögren's syndrome (SjS), the regulatory roles of non-canonical inflammasomes, such as mouse caspase-11 and human caspase-4 non-canonical inflammasomes, in these diseases are still largely unknown. Interestingly, an increasing number of studies have reported possible roles for non-canonical inflammasomes in the pathogenesis of various mouse models of rheumatic disease. This review comprehensively summarizes and discusses recent emerging studies demonstrating the regulatory roles of non-canonical inflammasomes, particularly focusing on the caspase-11 non-canonical inflammasome, in the pathogenesis and progression of various types of rheumatic diseases and provides new insights into strategies for developing potential therapeutics to prevent and treat rheumatic diseases as well as associated diseases by targeting non-canonical inflammasomes.
Inflammation represents the first-line defense mechanism of the host against pathogens and cellular stress. One of the most critical inflammatory responses is characterized by the activation of ...inflammasomes, intracellular multiprotein complexes that induce inflammatory signaling pathways in response to various pathogen-associated molecular patterns or danger-associated molecular patterns under physiological and pathological conditions. Inflammasomes are tightly regulated in normal cells, and dysregulation of these complexes is observed in various pathological conditions, especially inflammatory diseases and cancers. Epigenetic regulation has been suggested as a key mechanism in modulating inflammasome activity, and microRNAs (miRNAs) have been implicated in the post-transcriptional regulation of inflammasomes. Therefore, miRNA-mediated epigenetic regulation of inflammasomes in pathological conditions has received considerable attention, and current strategies for targeting inflammasomes have been shown to be effective in the treatment of diseases associated with inflammasome activation. This review summarizes recent studies suggesting the roles of miRNAs in the epigenetic control of inflammasomes and highlights the potential of miRNAs as a therapeutic tool for treating human diseases.
•Inflammasomes are key players in inflammatory responses and immunopathologies.•miRNAs directly target inflammasomes by binding with 3’-UTR of inflammasome genes.•miRNAs indirectly target inflammasomes by binding with 3’-UTR of other genes that regulate inflammasome expression.•miRNA-based therapeutics have great potential for the treatment of diseases linked to inflammasome dysfunction.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogenic virus that causes coronavirus disease 2019 (COVID-19), with major symptoms including hyper-inflammation and cytokine ...storm, which consequently impairs the respiratory system and multiple organs, or even cause death. SARS-CoV-2 activates inflammasomes and inflammasome-mediated inflammatory signaling pathways, which are key determinants of hyperinflammation and cytokine storm in COVID-19 patients. Additionally, SARS-CoV-2 inhibits inflammasome activation to evade the host's antiviral immunity. Therefore, regulating inflammasome initiation has received increasing attention as a preventive measure in COVID-19 patients. Ginseng and its major active constituents, ginsenosides and saponins, improve the immune system and exert anti-inflammatory effects by targeting inflammasome stimulation. Therefore, this review discussed the potential preventive and therapeutic roles of ginseng in COVID-19 based on its regulatory role in inflammasome initiation and the host's antiviral immunity.
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Inflammation represents the innate immune response of the body tissues against invading microbes and cellular danger signals, and, in this way, it is beneficial ....
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