Role of NLRP3 inflammasome in the periapical lesion development dynamics in wild-type and knockout animals

Abstract

Inflammasome is a multiprotein complex that aim to trigger caspase-1 activation and, consequently, cleave interleukins as IL-1² and IL-18. This complex has been studied in different systemic diseases as therapeutic target. The modulation of inflammasomes components could change or favor the resolution of those diseases. Thus, the aim of this study will be to evaluate the role of NLRP3 inflammasome in the dynamics of apical periodontitis (AP) development induced in mouse teeth. For this aim, the present study will be divided in 2 stages. On Stage 1, the specific aim will be evaluated the NLRP3 participation in the formation and development of AP in wild-type (with or without a NLRP3-specific inhibitory medication) knockout animals (NLRP3-/-). For Stage 1, will be performed microscopic evaluation (HE for description of inflammatory process and immunohistochemistry for macrophages, neutrophils, IL-1², IL-18, and Caspase-1); computed micro-tomography (¼-CT) to measure the AP; qRT-PCR for gene expression of IL-1², IL-18, NLRP3 and caspase-1; and TRAP for osteoclasts quantification. On Stage 2, the aim will be the evaluation of pyroptosis and microvesicles release, as IL-1² release pattern, in AP induced in NLRP3-/- and WT animals, performing qRT-PCR to quantify GSDM-D and P2X7, respectively. Data will be analyzed using the Graph Pad Prism 7 statistical program, using the appropriate tests for each evaluation (±= 5%). (AU)