ABSTRACT
Objective: To explore the relationship between NLRP3-mediated pyroptosis and olfactory dysfunction (OD) in allergic rhinitis (AR), and to evaluate the therapeutic potential of CY-09, a selective NLRP3 inhibitor for OD. Methods: An AR mouse model was established with ovalbumin, and the olfactory function of AR mice was detected by the buried food pellet test. Mice with OD were intraperitoneally injected with CY-09 or saline. The activation of microglia and astrocytes in olfactory bulb was detected by immunohistochemistry. The expression level of pyroptosis associated protein was detected by Western blot. The level of pyroptosis associated proinflammatory factor mRNA was determined by real-time PCR. SPSS 24.0 software was used for statistical analysis. Results: After the test, ovalbumin successfully established AR mice model, in which 52.5% (21/40) of them showed OD. The number of activated microglia and astroglia in olfactory bulb tissue in OD group were more than those in non-OD group (all P<0.05). Compared with the control group, the expression of NLRP3, caspase-1 and gasdermin D (GSDMD) was significantly increased in the olfactory bulb of the OD group (all P<0.05). CY-09 could significantly reduce the level of NLRP3, caspase-1, GSDMD, IL-1β and IL-18 expression, and inhibite the activation of microglia and astrocytes in the olfactory bulb tissues (all P<0.05). Conclusion: NLRP3-mediated pyroptosis is closely related to the OD associated with AR. CY-09 could improve the olfactory function in AR mice, which may be related to blocking the NLRP3-mediated pyroptosis.
Subject(s)
Animals , Humans , Mice , Caspases/therapeutic use , Disease Models, Animal , Inflammasomes/therapeutic use , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Ovalbumin , Pyroptosis , Rhinitis, Allergic/drug therapy , SmellABSTRACT
ABSTRACT Objective To determine if considering inflammasome NLRP3 as a treatment option for kidney disease is possible. Methods Literature review related to NLRP3 inflammasome structure, biological function and relationship with renal disease and others (hypertension, diabetes, gout, atherosclerosis, amyloidosis, Alzheimer's disease); the systematic review was made searching in the databases PubMed and SciELO for the following terms: "The NLRP3 inflammasome therapeutic for kidney disease", "NLRP3 nflammasome in kidney disease" in PubMed, and "Inflammasome" for Scielo. Results 146 documents were found, althoughonly 34 matched the working hypothesis concerning the NLRP3 inflammasome as a central component of various diseases in humans, with potential therapeutic use. The NLRP3 inflammasome is responsible for the maturation of inflammatory pro-interleukin IL-1 β and IL-18, which can be triggered by aggregated or crystalline materials (particles), and by various microorganisms and toxins derived from these; however, the way how activation mechanisms work is not completely clear. Conclusions Research on new therapies that focus on removing or inhibiting inflammasome components, both individually and together, is proposed.(AU)
RESUMEN Objetivo Determinar si el inflamasoma NLRP3 puede considerarse como opción de tratamiento para la enfermedad renal. Métodos Con el fin de encontrar bibliografía relacionada con la estructura del inflamasoma NLRP3, su función biológica y su relación con la enfermedad renal y otras (hipertensión, diabetes, gota, aterosclerosis, amiloidosis, enfermedad de Alzheimer), se realizó una revisión sistemática en dos bases de datos (PubMed y SciELO) con los términos: "NLRP3 inflammasome therapeutic for kidney disease" y "NLRP3 inflammasome in kidney disease" en PubMed, e "Iinflammasome" en SciELO. Resultados Se encontró un total de 146 documentos, de los cuales solo 34 concuerdan con la hipótesis de trabajo desarrollada con relación al inflamasoma NLRP3 como componente central de diversas enfermedades en seres humanos y con potencial uso terapéutico. El inflamasoma NLRP3 es responsable de la maduración de la interleucina inflamatoria pro-IL-1 β y IL-18, l cual puede darse por causa de materiales agregados o cristalinos (partículas), y por diversos microorganismos y toxinas derivadas de los mismos; sin embargo, los mecanismos de activación de este proceso siguen sin ser claros en la actualidad. Conclusiones Se propone estudiar nuevas terapias que se centren en la eliminación o inhibición de los componentes inflamasoma, de manera individual y conjunta.(AU)