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NLRP12 attenuates ozone-induced pulmonary inflammation by regulating canonical NF-κB Pathway
- Source :
- Ecotoxicology and Environmental Safety, Vol 262, Iss , Pp 115275- (2023)
- Publication Year :
- 2023
- Publisher :
- Elsevier, 2023.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 01476513
- Volume :
- 262
- Issue :
- 115275-
- Database :
- Directory of Open Access Journals
- Journal :
- Ecotoxicology and Environmental Safety
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.776800d42fca4cbdabd00431a55c32e2
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.ecoenv.2023.115275