NLRP3 inflammasome activation involved in LPS and coal tar pitch extract‐induced malignant transformation of human bronchial epithelial cells

2019 ◽  
Vol 34 (5) ◽  
pp. 585-593 ◽  
Author(s):  
Shuyin Duan ◽  
Na Wang ◽  
Li Huang ◽  
Hua Shao ◽  
Peng Zhang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Malignant Transformation ◽  
Nlrp3 Inflammasome ◽  
Coal Tar ◽  
Bronchial Epithelial Cells ◽  
Coal Tar Pitch ◽  
Inflammasome Activation ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Nlrp3 Inflammasome Activation

scholarly journals ANXA3 regulates HIF1α-induced NLRP3 inflammasome activity and promotes LPS-induced inflammatory response in bronchial epithelial cells

2021 ◽  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Response ◽  
Nlrp3 Inflammasome ◽  
Hypoxia Inducible Factor ◽  
Bronchial Epithelial Cells ◽  
Inflammasome Activation ◽  
Bronchial Epithelial ◽  
Asthmatic Patients ◽  
Pediatric Diseases ◽  
Inflammasome Activity

Introduction: Childhood asthma is one of the most common pediatric diseases, and its incidence is increasing. Annexin A3 (ANXA3) is a member of the Annexin family, a well-known polygenic family of membrane binding proteins. Bioinformation analysis showed that ANXA3 was highly expressed in asthmatic patients, suggesting the effects of ANXA3 on asthma, whereas the mechanism is still unclear. Methods: A inflammatory response model of bronchial epithelial BEAS-2B cells induced by LPS was constructed. Immunoblot and quantitative PCR assays were performed to detect the expression levels of ANXA3 in control or LPS-induced BEAS-2B cells. MTT, flow cytometry (FCM), and Immunoblot assays were respectively conducted to detect the effects of ANXA3 on survival and apoptosis of LPS-induced BEAS-2B cells. qPCR and ELISA assays were performed to detect the expression of TNF-α, IL-6, and IL-8. Additionally, Immunoblot assays were performed to detect the effects of ANXA3 on HIF1α and NLRP3 inflammasome in BEAS-2B cells. Results: We found ANXA3 was overexpressed in LPS-induced BEAS-2B cells. ANXA3 ablation promoted the survival of LPS-induced BEAS-2B cells and suppressed the inflammatory response of LPS-induced BEAS-2B cells. Importantly, we noticed ANXA3 inhibited HIF1α-induced NLRP3 inflammasome activity, and increasing the expression of HIF-α rescued the effects of ANXA3 depletion on asthma. Conclusion: ANXA3 enhanced LPS-triggered inflammation of human bronchial epithelial cells by regulating hypoxia-inducible factor-1α (HIF1α)-mediated NLRP3 inflammasome activation, and thought ANXA3 as a promising molecular target for acute asthma treatment.

scholarly journals Involvement of p53 Mutation and Mismatch Repair Proteins Dysregulation in NNK-Induced Malignant Transformation of Human Bronchial Epithelial Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Ying Shen ◽  
Shuilian Zhang ◽  
Xiaobin Huang ◽  
Kailin Chen ◽  
Jing Shen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Malignant Transformation ◽  
P53 Mutation ◽  
Bronchial Epithelial Cells ◽  
Genome Integrity ◽  
Human Bronchial Epithelial Cells ◽  
Cellular Functions ◽  
Independent Manner ◽  
Bronchial Epithelial ◽  
Cycle Arrest

Genome integrity is essential for normal cellular functions and cell survival. Its instability can cause genetic aberrations and is considered as a hallmark of most cancers. To investigate the carcinogenesis process induced by tobacco-specific carcinogen NNK, we studied the dynamic changes of two important protectors of genome integrity, p53 and MMR system, in malignant transformation of human bronchial epithelial cells after NNK exposure. Our results showed that the expression of MLH1, one of the important MMR proteins, was decreased early and maintained the downregulation during the transformation in a histone modification involved and DNA methylation-independent manner. Another MMR protein PMS2 also displayed a declined expression while being in a later stage of transformation. Moreover, we conducted p53 mutation analysis and revealed a mutation at codon 273 which led to the replacement of arginine by histidine. With the mutation, DNA damage-induced activation of p53 was significantly impaired. We further reintroduced the wild-type p53 into the transformed cells, and the malignant proliferation can be abrogated by inducing cell cycle arrest and apoptosis. These findings indicate that p53 and MMR system play an important role in the initiation and progression of NNK-induced transformation, and p53 could be a potential therapeutic target for tobacco-related cancers.

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