Animals ; Humans ; Inflammasomes ; Liver Diseases ; pathology

As a form of new programmed cell death, pyroptosis is divided into a canonical pyroptosis pathway and a non-canonical pyroptosis pathway. In recent years, it is reported that non-canonical pyroptosis is closely related to inflammatory reactions, which directly affects the occurrence, development, and outcome of sepsis, inflammatory bowel disease, respiratory disease, nerve system inflammatory disease, and other inflammatory diseases. When the cells were infected with Gram-negative bacteria or lipopolysaccharide (LPS), it can induce the activation of cysteinyl aspartate specific proteinase(caspase)-4/5/11 and directly bind to the cells to cleave gasdermin D (GSDM-D) into the active amino-terminus of GSDM-D. The amino-terminus of GSDM-D with membrane punching activity migrates to the cell membrane, triggering the rupture of the cell membrane, and the cell contents discharge, leading to the occurrence of non-canonical pyroptosis. After activation of caspase-11, it also promotes the canonical pyroptosis, activates and releases interleukin-1β and interleukin-18, which aggravated inflammation. Caspase-4/5/11, GSDM-D, Toll-like receptor 4 and high mobility group protein B1 are the key molecules of the non-canonical pyroptosis. Exploring the mechanisms of non-canonical pyroptosis and the related research progresses in inflammatory diseases intensively is of great significance for clinical prevention and treatment of the relevant diseases.
Caspases ; Humans ; Inflammasomes ; Inflammation ; Lipopolysaccharides ; Pyroptosis ; Sepsis

Type 1 diabetes is one of the classical examples of organ- specific autoimmune diseases characterized by lymphocytic infiltration or inflammation in pancreatic islets called 'insulitis'. In contrast, type 2 diabetes has been traditionally regarded as a metabolic disorder with a pathogenesis that is totally different from that of type 1 diabetes. However, recent investigation has revealed contribution of chronic inflammation in the pathogenesis of type 2 diabetes. In addition to type 2 diabetes, the role of chronic inflammation is being appreciated in a wide variety of metabolic disorders such as obesity, metabolic syndrome, and atherosclerosis. In this review, we will cover the role of innate immunity in the pathogenesis of metabolic disorders with an emphasis on NLRP3.
Atherosclerosis ; Autoimmune Diseases ; Immunity, Innate ; Inflammasomes ; Inflammation ; Islets of Langerhans ; Obesity

Type 1 diabetes is one of the classical examples of organ- specific autoimmune diseases characterized by lymphocytic infiltration or inflammation in pancreatic islets called 'insulitis'. In contrast, type 2 diabetes has been traditionally regarded as a metabolic disorder with a pathogenesis that is totally different from that of type 1 diabetes. However, recent investigation has revealed contribution of chronic inflammation in the pathogenesis of type 2 diabetes. In addition to type 2 diabetes, the role of chronic inflammation is being appreciated in a wide variety of metabolic disorders such as obesity, metabolic syndrome, and atherosclerosis. In this review, we will cover the role of innate immunity in the pathogenesis of metabolic disorders with an emphasis on NLRP3.
Atherosclerosis ; Autoimmune Diseases ; Immunity, Innate ; Inflammasomes ; Inflammation ; Islets of Langerhans ; Obesity

Pyroptosis is a novel type of programmed cell death, which is closely related with the pathogenesis of myelodysplastic syndromes (MDS). The recent studies showed that all of S100A9/TLR4, S100A9/CD33 and Nox/ROS signaling pathways can activate oxygen-sensitivity NLRP3 inflammasome and then induce the pyroptosis of hematopoeitic stem cells (HSC) / hematopeitic pregenitor cells (HPC), resulting in ineffective hematopoiesis in patients with MDS. Further studies on the role and molecular mechanism of pyroptosis in the pathogenesis of MDS will provide the potential opportunity for the diagnosis and treatment of MDS. Here, the recent advances in the role and mechnism of pyroptosis in the pathogenesis of MDS are reviewed.
Hematopoiesis ; Humans ; Inflammasomes ; Myelodysplastic Syndromes ; Pyroptosis ; Signal Transduction

Flavonoids are major plant constituents with numerous biological/pharmacological actions both in vitro and in vivo. Of these actions, their anti-inflammatory action is prominent. They can regulate transcription of many proinflammatory genes such as cyclooxygenase-2/inducible nitric oxide synthase and many cytokines/chemokines. Recent studies have demonstrated that certain flavonoid derivatives can affect pathways of inflammasome activation and autophagy. Certain flavonoids can also accelerate the resolution phase of inflammation, leading to avoiding chronic inflammatory stimuli. All these pharmacological actions with newly emerging activities render flavonoids to be potential therapeutics for chronic inflammatory disorders including arthritic inflammation, meta-inflammation, and inflammaging. Recent findings of flavonoids are summarized and future perspectives are presented in this review.
Autophagy ; Flavonoids ; In Vitro Techniques ; Inflammasomes ; Inflammation ; Nitric Oxide Synthase ; Plants

Inflammatory injury of the intestine is often accompanied by symptoms such as damage to intestinal mucosa, increased intestinal permeability, and intestinal motility dysfunction. Inflammatory factors spread throughout the body via blood circulation, and can cause multi-organ failure. Pyroptosis is a newly discovered way of programmed cell death, which is mainly characterized by the formation of plasma membrane vesicles, cell swelling until the rupture of the cell membrane, and the release of cell contents, thereby activating a drastic inflammatory response and expanding the inflammatory response cascade. Pyroptosis is widely involved in the occurrence of diseases, and the underlying mechanisms for inflammation are still a hot spot of current research. The caspase-1 mediated canonical inflammasome pathway of pyroptosis and caspase-4/5/8/11-mediated non-canonical inflammasome pathway are closely related to the occurrence and development of intestinal inflammation. Therefore, investigation of the signaling pathways and molecular mechanisms of pyroptosis in intestinal injury in sepsis, inflammatory bowel diseases, infectious enteristic, and intestinal tumor is of great significance for the prevention and treatment of intestinal inflammatory injury.
Humans ; Pyroptosis ; Inflammasomes/metabolism* ; Apoptosis ; Caspase 1 ; Inflammation

Mitochondria are key organelles involved in energy production, functioning as the metabolic hubs of cells. Recent findings emphasize the emerging role of the mitochondrion as a key intracellular signaling platform regulating innate immune and inflammatory responses. Several mitochondrial proteins and mitochondrial reactive oxygen species have emerged as central players orchestrating the innate immune responses to pathogens and damaging ligands. This review explores our current understanding of the roles played by mitochondria in regulation of innate immunity and inflammatory responses. Recent advances in our understanding of the relationship between autophagy, mitochondria, and inflammasome activation are also briefly discussed. A comprehensive understanding of mitochondrial role in toll-like receptor-mediated innate immune responses and NLRP3 inflammasome complex activation, will facilitate development of novel therapeutics to treat various infectious, inflammatory, and autoimmune disorders.
Autophagy ; Immunity, Innate* ; Inflammasomes ; Inflammation* ; Ligands ; Mitochondria ; Mitochondrial Proteins ; Organelles ; Reactive Oxygen Species

The aim of this study was to determine the association between P2X7R rs3751142 and CARD8 rs2043211 polymorphisms and gout susceptibility in male Korean subjects. This study enrolled a total of 242 male patients with gout and 280 healthy controls. The polymorphisms of two individual genes including rs3751142(C>A) in the P2X7R gene and rs2043211(A>T) in the CARD8 gene were assessed using Taq-Man analysis. Statistical analyses were performed using the Chi-square test, Kruskal-Wallis test, and logistic regression analyses. A difference in genotypic frequency of the P2X7R rs3751142 and CARD8 rs2043211 genes was not detected between gout and control patients. Clinical parameters including age, onset age, disease duration, body mass index, and serum uric acid levels were not different among the three genotypes for either P2X7R or CARD8 (P > 0.05 for all). A pair-wise comparison of P2X7R rs3751142 and CARD8 rs2043211 genotype combinations revealed that subjects with the CA P2X7R rs3751142 genotype and the TT CARD8 rs2043211 genotype had a trend toward a higher risk of gout compared to the CC/AA combination (P = 0.056, OR = 2.618, 95% CI 0.975 - 7.031). In conclusion, this study revealed that genetic variability of the P2X7R rs3751142 and CARD8 rs2043211 genes might, in part, be associated with susceptibility for gout.
Age of Onset ; Body Mass Index ; Genotype ; Gout* ; Humans ; Inflammasomes ; Logistic Models ; Male ; Uric Acid

Among a number of innate receptors, the nucleotide-binding domain leucine-rich repeat containing (NLR) nucleotide oligomerization domain (NOD)-like receptor families are involved in the recognition of cytosolic pathogen- or danger-associated molecules. Activation of these specific sets of receptors leads to the assembly of a multiprotein complex, the inflammasome, leading to the activation of caspase-1 and maturation of the cytokines interleukin (IL)-1beta, IL-18, and IL-33. Among NLRs, NLR-related protein 3 (NLRP3) is one of the best-characterized receptors that activates the inflammasome. There is no doubt that NLRP3 inflammasome activation is important for host defense and effective pathogen clearance against fungal, bacterial, and viral infection. In addition, mounting evidence indicates that the NLRP3 inflammasome plays a role in a variety of inflammatory diseases, including gout, atherosclerosis, and type II diabetes, as well as under conditions of cellular stress or injury. Here, we review recent advances in our understanding of the role of the NLRP3 inflammasome in host defense and various inflammatory diseases.
Atherosclerosis ; Cytokines ; Cytosol ; Defense Mechanisms ; Gout ; Humans ; Inflammasomes ; Inflammation ; Interleukin-18 ; Interleukins