Vitamin D3 protects against nitrogen mustard-induced apoptosis of the bronchial epithelial cells via activating the VDR/Nrf2/Sirt3 pathway

2021 ◽  
Author(s):  
Wenpei Yu ◽  
Xunhu Dong ◽  
Guorong Dan ◽  
Feng Ye ◽  
Jin Cheng ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Vitamin D3 ◽  
Nitrogen Mustard ◽  
Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Induced Apoptosis

scholarly journals Corticosteroids, eosinophils and bronchial epithelial cells: new insights into the resolution of inflammation in asthma

2003 ◽  
Vol 178 (1) ◽  
pp. 37-43 ◽  
Author(s):  
GM Walsh ◽  
DW Sexton ◽  
MG Blaylock
Keyword(s):  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Bronchial Epithelial Cells ◽  
Membrane Receptors ◽  
Bronchial Epithelial ◽  
Anti Inflammatory ◽  
Macrophage Colony ◽  
High Doses ◽  
Induced Apoptosis ◽  
Receptor Ligation

Anti-inflammatory therapy in asthma is reliant on corticosteroids, particularly in their inhaled form. However, steroids are rather non-specific in their actions and they also raise concerns regarding compliance and side-effect Issues. Furthermore, a small proportion of patients with asthma fail to respond to oral glucocorticoids even at high doses. This Article will review the role that steroids and membrane receptor ligation play in the induction of eosinophil apoptosis together with the mechanisms by which corticosteroids enhance the disposal of apoptotic eosinophils by both professional and non-professional phagocytes. Eosinophils are thought to be the major pro-inflammatory effector cell in asthma and their persistence in the airways is probably enhanced by the presence of several asthma-relevant cytokines that prolong eosinophil survival by inhibition of apoptosis (interleukin (IL)-3, IL-5, granulocyte-macrophage colony-stimulating factor, IL-9, IL-13, IL-15). In contrast, a number of signals have been described that accelerate apoptosis in human eosinophils including corticosteroids or ligation of membrane receptors (CD95, CD45, CD69). Thus, the load of lung eosinophils in asthmatic disease is likely to be related to a balance in the tIssue microenvironment between pro- and anti-apoptotic signals. Furthermore, removal of apoptotic eosinophils by phagocytosis by alveolar macrophages or bronchial epithelial cells in a specific receptor-mediated way is as important as the process of apoptosis induction. Corticosteroids enhance the recognition and engulfment of apoptotic eosinophils by macrophages or bronchial epithelial cells. Caspases are key intracellular molecules in the control of apoptosis and defects in caspase-induced apoptosis in eosinophils from steroid-resistant individuals may contribute to the molecular mechanisms underlying glucocorticoid insensitivity in these cells. These findings point the way to new and more targeted anti-inflammatory therapy for asthma and may provide important clues for the development of alternative therapies for glucocorticoid resistance.

scholarly journals Curcumin Inhibits Heat-Induced Apoptosis by Suppressing NADPH Oxidase 2 and Activating the Akt/mTOR Signaling Pathway in Bronchial Epithelial Cells

2017 ◽  
Vol 41 (5) ◽  
pp. 2091-2103 ◽  
Author(s):  
Yuan Peng ◽  
Junliang Pu ◽  
Chengyong Tang ◽  
Zhongjun Wu
Keyword(s):  
Epithelial Cells ◽  
Nadph Oxidase ◽  
Bronchial Epithelial Cell ◽  
Inhalation Injury ◽  
Bronchial Epithelial Cells ◽  
Mtor Signaling Pathway ◽  
Bronchial Epithelial ◽  
Nadph Oxidase 2 ◽  
Induced Apoptosis

Background: Heat causes bronchial epithelial cell apoptosis, which is a known factor contributing to airway damage during inhalation injury. Accumulating evidence has shown the effect of curcumin on inhibiting apoptosis. In this study, we investigated whether curcumin suppresses heat-induced apoptosis in bronchial epithelial cells and the underlying mechanism. Methods: Bronchial epithelial cell line 16HBE140 cells were incubated at either 42 °C, 47 °C, 52 °C, or 57 °C for 5 min in a cell incubator and then returned back to normal culture conditions (37 °C). An in vivo thermal inhalation injury rat model was established with a heat gun blowing hot air into the airway of rats. 16HBE140 cells and lung tissue were obtained for further study with or without curcumin treatment. Cell viability was determined by measuring the absorbance of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). 2',7'-dichlorofluorescein diacetate fluorescence was used as a measure of reactive oxygen species (ROS) production. Levels of Bcl2, Bax, α-ATP, cleaved Poly (ADP-ribose) polymerase (PARP), cleaved caspase-3, gp91phox, p47phox, p67phox, p22phox, p40phox, and Rac were determined by Western blotting. TUNEL staining was used to determine apoptosis. Results: Heat treatment triggered the apoptosis of 16HBE140 cells as shown by the increase in apoptosis molecular markers, including Bcl-2, Bax, cleaved PARP, and cleaved caspase-3. Administration of curcumin significantly inhibited apoptosis of 16HBE140 cells and suppressed the membrane translocation of NADPH oxidase 2 cytosolic components, as well as ROS production. Downregulation of Akt and mTOR phosphorylation induced by heat was also reversed by curcumin. Furthermore, we demonstrated that NADPH oxidase 2 is upstream of Akt/mTOR in heat-induced apoptosis. The protective role of curcumin on bronchial epithelia apoptosis was also confirmed in vivo by a rat inhalation injury model. Conclusion: This study demonstrates that one of the critical mechanisms underlying curcumin inhibiting heat-induced apoptosis is through suppressing NADPH Oxidase 2 and activating the Akt/mTOR signaling pathway in bronchial epithelial cells.

Simultaneous inactivation of GSK-3β suppresses quercetin-induced apoptosis by inhibiting the JNK pathway

2013 ◽  
Vol 304 (11) ◽  
pp. L782-L789 ◽  
Author(s):  
Kyoung-Hee Lee ◽  
Chul-Gyu Yoo
Keyword(s):  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Bronchial Epithelial Cells ◽  
Dependent Manner ◽  
Bronchial Epithelial ◽  
Anti Inflammatory ◽  
Gsk 3Β ◽  
Induced Apoptosis ◽  
Jnk Activation

Quercetin, a ubiquitous bioactive plant flavonoid, has shown to exert a broad range of activities, such as apoptotic, antioxidant, and anti-inflammatory effects. Thus, flavonoids can mediate both cell protection and cell injury. Recently, quercetin has been reported to prevent the progression of emphysema in animal models through antioxidant and anti-inflammatory actions. These findings suggest that quercetin could be a potential treatment option for chronic obstructive pulmonary disease. Its clinical application, however, could be limited by the cytotoxicity of quercetin, and understanding of the apoptotic mechanisms of quercetin is a prerequisite to develop a therapeutic strategy with minimal cytotoxicity. We evaluated the apoptotic effect of quercetin and its molecular mechanisms in normal bronchial epithelial cells (BEAS-2B cells). Quercetin decreased the viability of BEAS-2B cells via apoptosis in a dose- and time-dependent manner. Quercetin activated JNK and increased the expression levels of c-Jun and p53-dependent Bax. Blockade of JNK activation by overexpression of dominant negative JNK1 suppressed apoptosis by quercetin via inhibition of caspase-3 activation and reduction of p53 and Bax expression. Simultaneously, quercetin inactivated glycogen synthase kinase (GSK)-3β, which is phosphatidylinositol 3-kinase/Akt dependent. Overexpression of a constitutively active GSK-3β mutant enhanced quercetin-induced JNK activation. In contrast, overexpression of enzymatically inert GSK-3β inhibited JNK activation, resulting in a suppression of apoptosis by quercetin. Taken together, the JNK-p53 pathway is involved in quercetin-induced apoptosis, and simultaneous inactivation of GSK-3β can attenuate apoptosis in normal bronchial epithelial cells.

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