Role of NLRP3 Inflammasome in Eosinophilic and Non-eosinophilic Chronic Rhinosinusitis with Nasal Polyps. 2016

Hai Lin, and Zhipeng Li, and Dong Lin, and Chunquan Zheng, and Weitian Zhang
Department of Otorhinolaryngology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China. lhi2012@sina.com.

The pathophysiologic mechanisms of human chronic rhinosinusitis with nasal polyps (CRSwNP) remain unclear. We aimed to elucidate expression and biologic role of NLRP3 inflammasome in CRSwNP. Immunohistochemistry (IHC) was conducted to assess NLRP3 immunolabeling, real-time polymerase chain reaction (PCR) was used for IL-9 and NLRP3, and caspase-1 level quantitation in CRSwNP and control subjects. In addition, enzyme-linked immunosorbent assay (ELISA) was employed for analyzing concentrations of IL-1β and IL-18 in the homogenates prepared from tissue specimens. Moreover, human nasal epithelial cells (HNECs) were used to evaluate the effects of lipopolysaccharide (LPS) and glyburide on NLRP3 inflammasome signaling pathway. Results showed that NLRP3 and caspase-1 were overexpressed in CRSwNP, especially in eosinophilic CRSwNP (ECRSwNP). Interestingly, NLRP3 expression had close correlation to that of caspase-1. Concentrations of IL-1β and IL-18 were elevated. NLRP3 inflammasome signaling pathway was augmented by LPS but suppressed by glyburide. In conclusion, NLRP3 inflammasome signaling pathway played a pro-inflammatory role in the pathogenesis of CRSwNP, especially in ECRSwNP. NLRP3 inflammasome signaling pathway was augmented by LPS, but suppressed by glyburide.

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
D009298 Nasal Polyps Focal accumulations of EDEMA fluid in the NASAL MUCOSA accompanied by HYPERPLASIA of the associated submucosal connective tissue. Polyps may be NEOPLASMS, foci of INFLAMMATION, degenerative lesions, or malformations. Nasal Polyp,Polyp, Nasal,Polyps, Nasal
D002908 Chronic Disease Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care (Dictionary of Health Services Management, 2d ed). For epidemiological studies chronic disease often includes HEART DISEASES; STROKE; CANCER; and diabetes (DIABETES MELLITUS, TYPE 2). Chronic Condition,Chronic Illness,Chronically Ill,Chronic Conditions,Chronic Diseases,Chronic Illnesses,Condition, Chronic,Disease, Chronic,Illness, Chronic
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D005905 Glyburide An antidiabetic sulfonylurea derivative with actions like those of chlorpropamide Glibenclamide,Daonil,Diabeta,Euglucon 5,Euglucon N,Glybenclamide,HB-419,HB-420,Maninil,Micronase,Neogluconin,HB 419,HB 420,HB419,HB420
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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
D012220 Rhinitis Inflammation of the NASAL MUCOSA, the mucous membrane lining the NASAL CAVITIES. Nasal Catarrh,Catarrh, Nasal,Catarrhs, Nasal,Nasal Catarrhs,Rhinitides
D012852 Sinusitis Inflammation of the NASAL MUCOSA in one or more of the PARANASAL SINUSES. Sinus Infections,Infection, Sinus,Infections, Sinus,Sinus Infection,Sinusitides
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal

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