NLRP12 attenuates ozone-induced pulmonary inflammation by regulating canonical NF-κB Pathway

Ozone (O₃) is an important urban air pollutant having strong correlations with respiratory diseases. Several lines of evidence suggest that O₃ exposure causes airway hyperresponsiveness (AHR) and pulmonary inflammation. Inhibitory innate immune receptors, such as NLRP12, have been demonstrated to alleviate inflammation, but the functional role for NLRP12 in O₃-induced lung inflammatory inflammation remains to be reported. Here, we determined whether NLRP12 took a protective role in O₃-induced AHR and pulmonary inflammation via the suppression of canonical NF-κB. C57BL/6 J mice were exposed to filtered air (FA) or 0.25, 0.50 and 1.00 ppm (3 h/day for 5 consecutive days) followed by detection of airway resistance, white blood cells, total proteins, and cytokines. Meanwhile, NLRP12 in lung tissue were detected by real time PCR. Moreover, we also examined protein expression of NLRP12 and key biomarkers of NF-κB pathway. It was shown that 24 h post O₃ exposure, AHR as wells as total cells, proteins, and cytokines contents in BALF of mice were increased compare to those of FA controls in a dose-dependent manner. Notably, O₃-induced AHR and lung inflammation were associated with significant decrease in pulmonary NLRP12 and upregulation of phosphorylated IRAK1, p65 and IκBα in canonical NF-κB pathway. Intratracheal administration of NLRP12-overexpresing adenovirus 4 days prior to O₃ exposure alleviated AHR and lung inflammation, and inhibited canonical NF-κB pathway activation. The findings from this study indicate that NLRP12 attenuates O₃-induced AHR and pulmonary inflammation, possibly through regulating canonical NF-κB pathway. This provides a novel target for the prevention and treatment of lung diseases induced by O₃ exposure.