Biomaterial Database

PSMB5 Alleviates Ulcerative Colitis by Inhibiting ROS-Dependent NLRP3 Inflammasome-Mediated Pyroptosis. 2022

Liang Han, and Yanping Hao, and Xudong Wu, and Duanmin Hu

Department of Gastroenterology, Second Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, China.

Ulcerative colitis (UC) is a chronic inflammatory disease. Intestinal mucosal injury is a significant factor in UC. Pyroptosis is a kind of programmed cell death induced by inflammatory caspases. Proteasome 20S subunit beta 5 (PSMB5) promotes cell viability. The purpose of this study was to determine the impact of PSMB5 on intestinal mucosal injury and to elucidate the underlying processes in dextran sulfate sodium- (DSS-) induced UC mice. Kunming (KM) mice received 3% DSS for 5 days to induce UC. We collected clinical symptoms, body weight, colon length, and histological changes. MDA (malondialdehyde) and SOD (superoxide dismutase) levels were determined using an ELISA assay. RT-PCR was used to assess the expression of IL-1β and IL-18. PSMB5 demonstrated a significant effect against UC by increasing body weight and colon length and decreasing DAI (disease activity index), colon macroscopic damage index (CMDI), histological injury scores, and reactive oxygen species (ROS), MDA, and SOD levels, thereby alleviating histopathological changes and inhibiting oxidative stress. HIEC-6 cells were exposed to lipopolysaccharide (LPS) condition with or without PSMB5, along with caspase-1 inhibitor (Z-VAD-FMK), NLRP3 inhibitor (MCC950), and ROS scavenger N-acetylcysteine (NAC). The viability of the cells, the release of lactate dehydrogenase (LDH), and intracellular ROS generation were determined using assay kits. Western blot analysis was used to determine the levels of NLRP3, ASC, cleaved caspase-1 (p20), pro-IL-1β, IL-1β, pro-IL-18, and IL-18. PSMB5 overexpression enhanced the inflammatory damage in LPS-treated HIEC-6 cells by activating the NLRP3 inflammasome and mediating pyroptosis, as demonstrated by increased LDH release and lower cell viability, as well as increased expression of NLRP3, ASC, cleaved caspase-1 (p20), IL-1, and IL-18. Meanwhile, NAC protected HIEC-6 cells from LPS-induced damage by reversing the activation of the NLRP3 inflammasome-mediated pyroptosis. In conclusion, PSMB5 may lower HIEC-6 cell susceptibility to LPS and ameliorate UC-induced HIEC-6 cell damage by decreasing ROS generation and hence inhibiting NLRP3-mediated pyroptosis.

UI	MeSH Term	Description	Entries
D008070	Lipopolysaccharides	Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)	Lipopolysaccharide,Lipoglycans
D001835	Body Weight	The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.	Body Weights,Weight, Body,Weights, Body
D003093	Colitis, Ulcerative	Inflammation of the COLON that is predominantly confined to the MUCOSA. Its major symptoms include DIARRHEA, rectal BLEEDING, the passage of MUCUS, and ABDOMINAL PAIN.	Colitis Gravis,Idiopathic Proctocolitis,Inflammatory Bowel Disease, Ulcerative Colitis Type,Ulcerative Colitis
D000069292	Pyroptosis	Type of programmed cell death associated with infection by intracellular pathogens. It is characterized by INFLAMMASOME formation; activation of CASPASE 1; and CYTOKINES mediated inflammation.	Caspase-1 Dependent Cell Death,Inflammatory Apoptosis,Pyroptotic Cell Death,Apoptoses, Inflammatory,Apoptosis, Inflammatory,Caspase 1 Dependent Cell Death,Cell Death, Pyroptotic,Cell Deaths, Pyroptotic,Death, Pyroptotic Cell,Deaths, Pyroptotic Cell,Inflammatory Apoptoses,Pyroptoses,Pyroptotic Cell Deaths
D000071199	NLR Family, Pyrin Domain-Containing 3 Protein	An NLR protein that contains an N-terminal PYRIN DOMAIN and ATP-binding site and 9 C-terminal LEUCINE-rich repeats; it is expressed primarily by MACROPHAGES. It is a core component of the INFLAMMASOME and directs its assembly in response to pathogen infection and damage-associated stimuli. Mutations in the NLRP3 gene are associated with FAMILIAL COLD AUTOINFLAMMATORY SYNDROME.	Cold Autoinflammatory Syndrome 1 Protein,NACHT, LRR and PYD Domains-Containing Protein 3,NLRP3 Protein,NACHT, LRR and PYD Domains Containing Protein 3,NLR Family, Pyrin Domain Containing 3 Protein
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013482	Superoxide Dismutase	An oxidoreductase that catalyzes the reaction between SUPEROXIDES and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide.	Hemocuprein,Ag-Zn Superoxide Dismutase,Cobalt Superoxide Dismutase,Cu-Superoxide Dismutase,Erythrocuprein,Fe-Superoxide Dismutase,Fe-Zn Superoxide Dismutase,Iron Superoxide Dismutase,Manganese Superoxide Dismutase,Mn-SOD,Mn-Superoxide Dismutase,Ag Zn Superoxide Dismutase,Cu Superoxide Dismutase,Dismutase, Ag-Zn Superoxide,Dismutase, Cobalt Superoxide,Dismutase, Cu-Superoxide,Dismutase, Fe-Superoxide,Dismutase, Fe-Zn Superoxide,Dismutase, Iron Superoxide,Dismutase, Manganese Superoxide,Dismutase, Mn-Superoxide,Dismutase, Superoxide,Fe Superoxide Dismutase,Fe Zn Superoxide Dismutase,Mn SOD,Mn Superoxide Dismutase,Superoxide Dismutase, Ag-Zn,Superoxide Dismutase, Cobalt,Superoxide Dismutase, Fe-Zn,Superoxide Dismutase, Iron,Superoxide Dismutase, Manganese
D017382	Reactive Oxygen Species	Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of SIGNAL TRANSDUCTION and GENE EXPRESSION, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.	Active Oxygen Species,Oxygen Radical,Oxygen Radicals,Pro-Oxidant,Reactive Oxygen Intermediates,Active Oxygen,Oxygen Species, Reactive,Pro-Oxidants,Oxygen, Active,Pro Oxidant,Pro Oxidants,Radical, Oxygen
D046988	Proteasome Endopeptidase Complex	A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.	20S Proteasome,Ingensin,Macropain,Macroxyproteinase,Multicatalytic Endopeptidase Complex,Multicatalytic Proteinase,Prosome,Proteasome,Complex, Multicatalytic Endopeptidase,Complex, Proteasome Endopeptidase,Endopeptidase Complex, Multicatalytic,Endopeptidase Complex, Proteasome,Proteasome, 20S,Proteinase, Multicatalytic
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus