NLRP3 Inflammasome Activation During Acute Negative Pressure Injury in the Middle Ear of Mice.

ABSTRACT

HYPOTHESIS: The present study was conducted to explore the role of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in mouse otic barotrauma models. BACKGROUND: Previous studies suggest that the NLRP3 inflammasome plays an important role in the pathogenesis of middle ear disease. However, whether middle ear negative pressure injury underlies NLRP3 inflammasome activation remains unclear. METHODS: Wild-type and Nlrp3 -/- mice were randomly assigned to control and pressure injury groups, respectively. Pressure loading was performed using a pressure cabin with the pressure level set to 20 kPa higher than that of the ambient atmosphere. This was achieved in approximately 15 seconds and maintained for 10 minutes. Hematoxylin and eosin staining was performed to detect morphological changes of the middle ear mucosa, tissue IL-1ß was measured via an enzyme-linked immunosorbent assay, and cleaved caspase-1 was detected by Western blot. RESULTS: We found that the maturation of caspase-1 and IL-1ß production in the middle ear significantly increased after otic barotrauma. In Nlrp3 -/- mice, inflammasome activation is downregulated and mucosal hyperplasia is reduced compared with those of wild-type mice during recovery. CONCLUSION: The NLRP3 inflammasome likely plays an important role in the pathogenesis of otic barotrauma. Controlling activation of the NLRP3 inflammasome may promote middle ear recovery after negative pressure injury.