Titanium Dioxide Aggravated Allergic Asthma Response Via Extracellular Traps Formation

Abstract

Titanium dioxide nanoparticles (nTiO2) play a critical role in promoting allergic airway inflammation, but the mechanism underlying in the immune response remains not well clarified. Extracellular traps (ETs) formation has been proved to be associated with exacerbation pathogenesis of allergic asthma. Thus, we aimed to investigate whether nTiO2 aggravated allergic asthma responses via ETs formation, and the potential molecule mechanism of these actions in nTiO2 aggravated allergic asthma response. BALB/c mice were sensitized with OVA via intraperitoneal injection. nTiO2 was intraperitoneally given before model induction. DNase Ι or PBS was intraperitoneally administered 10 minutes on days 0, 7, 14, 21, 22 and 23 before OVA administration. Lung tissue and bronchoalveolar lavage fluid (BALF) were collected for histologic analysis, cytokine examining and NETs quantitation. Morphologic quantitative analysis of nTiO2-induced ETs was observed by fluorescence confocal microscopy, and the quantitation of nTiO2-induced ETs was determined by Pico Green and a fluorometric reader. The results showed that nTiO2 administration induced severe pathological features of allergic asthma responses and IL-4 and IL-13 levels than OVA. Furthermore, nTiO2 promoted pulmonary ETs release in OVA-induced allergic asthma, which was degraded by DNase I. Besides adjuvant effects of nTiO2 in OVA-induced allergic asthma, nTiO2 also directly induced ETs release in vivo and in vitro, which reveal that nTiO2 may also directly induced immune responses through ETs formation. All these results suggest that strategies against ETs release might be helpful for treatment of nTiO2- provoted inflammatory response in OVA-induced allergic asthma. Funding Statement: This work was funded by the National Natural Science Foundation of China (No.31572583, 31602122). Declaration of Interests: No conflict of interest. Ethics Approval Statement: Animal experiments were approved by the Care and Use of Laboratory Animals of the Jilin University and in line with the current Animal Protection Laws of China.