Is NLRP3 or NLRP6 inflammasome activation associated with inflammation-related lung tumorigenesis induced by benzo(a)pyrene and lipopolysaccharide?

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ID: 53275
2019
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Abstract
Chronic inflammation has been shown to play a vital role in lung tumorigenesis. Recently, we have successfully developed a C57BL/6 mouse model of inflammation-related lung tumorigenesis induced by benzo(a)pyrene [B(a)p] and lipopolysaccharide (LPS), which will contribute to better understand the association between pulmonary inflammation and cancer. In this study, we aim to explore the role of NLRP3 and NLRP6 inflammasome in lung tumorigenesis in the animal model that we set up previously. Levels of NLRP3, NLRP6, interleukin-1β (IL-1β) and IL-18 protein in lung tissues were detected by using immunohistochemistry. The co-localization of NLRP3 or NLRP6 with caspase-1 was examined using immunofluorescence and confocal. Western blotting was used to evaluate the levels of caspase-1 p10 and cleaved-IL-1β protein. The expression of IL-18 in bronchoalveolar lavage fluid (BALF) was measured using ELISA kit. The expression of NLRP3, NLRP6 and IL-18 protein in the lung tissues of mice exposed to B(a)p plus LPS was upregulated significantly compared with those in Vehicle control group. Immunofluorescent results indicated the co-localization of NLRP3 with caspase-1 was increased in the lung tissues of LPS-, B(a)p- or B(a)p plus LPS-exposed mice than that in Vehicle control group, but no co-localization of NLRP6 with caspase-1. Additionally, caspase-1 activation was induced, cleaved-IL-1β in lung tissues and IL-18 protein in BALF were increased in B(a)p plus LPS-exposed mice compared with those in B(a)p group. In conclusion, our results from this study demonstrate that NLRP3 inflammasome, not NLRP6 inflammasome, activation is involved in B(a)p plus LPS-induced inflammation-related lung tumorigenesis in mice, but the mechanisms of NLRP6 participate in the development of lung cancer should be further investigated.
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gao2019isecotoxicology Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Gao, Min;Zhang, Peng;Huang, Li;Shao, Hua;Duan, Shuyin;Li, Chunyang;Zhang, Qiao;Wang, Wei;Wu, Yongjun;Wang, Jing;Liu, Hong;Feng, Feifei;
Journal Ecotoxicology and environmental safety
Year 2019
DOI
S0147-6513(19)31018-8
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