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Epithelium-derived IL17A Promotes Cigarette Smoke-induced Inflammation and Mucus Hyperproduction
In this study, we aim to determine whether epithelial-derived IL17A regulates inflammation and mucus hyperproduction in COPD using a cultured human bronchial epithelial (HBE) cell line in vitro and airway epithelium IL17A-specific knockout mouse in vivo. Increased IL17A expression was observed in mouse airway epithelium upon cigarette smoke (CS) exposure or in a COPD mouse model that was induced by CS and elastin. CS extract (CSE) also triggered IL17A expression in HBE cells. Blocking IL17A or IL17RA effectively attenuated CSE-induced MUC5AC and the inflammatory cytokines IL6, tumor necrosis factor (TNF)-α, and IL1β in H...
Source: Am J Respir Cell Mol... - June 29, 2021 Category: Respiratory Medicine Authors: Mindan Wu Tianwen Lai Du Jing Shiyi Yang Yanping Wu Zhouyang Li Yinfang Wu Yun Zhao Lingren Zhou Haipin Chen Jiaxin Shen Wen Li Songmin Ying Zhihua Chen Xiaohong Wu Huahao Shen Source Type: research

Cigarette Smoke Activates NOTCH3 to Promote Goblet Cell Differentiation in Human Airway Epithelial Cells.
The objective of this study was to determine whether NOTCH signaling regulates goblet cell differentiation in response to cigarette smoke. Primary human bronchial epithelial cells (HBECs) from nonsmokers and COPD smokers were differentiated in vitro on air-liquid interface and exposed to cigarette smoke extract (CSE) for 7 days. NOTCH signaling activity was modulated using (1) the NOTCH/γ-secretase inhibitor Dibenzazepine (DBZ), (2) lentiviral over-expression of the NOTCH3-intracellular domain (NICD3) or (3) NOTCH3-specific siRNA. Cell differentiation and response to CSE were evaluated by qPCR, Western blotting, immunosta...
Source: Am J Respir Cell Mol... - January 14, 2021 Category: Respiratory Medicine Authors: Bodas M, Moore AR, Subramaniyan B, Georgescu C, Wren JD, Freeman WM, Brown BR, Metcalf JP, Walters MS Tags: Am J Respir Cell Mol Biol Source Type: research

CARM1 Regulates Alveolar Epithelial Senescence and Elastase-induced Emphysema Susceptibility.
Abstract Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible loss of lung function and is one of the most prevalent and severe diseases world-wide. A major feature of COPD is emphysema -the progressive loss of alveolar tissue. Coactivator-associated arginine methyltransferase-1 (CARM1) regulates histone-methylation and the transcription of genes involved in senescence, proliferation and differentiation. Complete loss of CARM1 leads to disrupted differentiation and maturation of alveolar epithelial type-II cells (ATII). We thus hypothesized that CARM1 regulates the development and progr...
Source: Am J Respir Cell Mol... - April 23, 2015 Category: Respiratory Medicine Authors: Sarker RS, John-Schuster G, Bohla A, Mutze K, Burgstaller G, Bedford MT, Königshoff M, Eickelberg O, Yildirim AÖ Tags: Am J Respir Cell Mol Biol Source Type: research

Real-time Imaging of ATP Release Induced by Mechanical Stretch in Human Airway Smooth Muscle Cells.
Abstract Airway smooth muscle (ASM) cells within the airway walls are continually exposed to mechanical stimuli and exhibit various functions in response to these mechanical stresses. ATP acts as an extracellular mediator in the airway. Moreover, extracellular ATP is considered to play an important role in the pathophysiology of asthma and chronic obstructive pulmonary disease. However, it is not known whether ASM cells are cellular sources of ATP secretion in the airway. We therefore investigated whether mechanical stretch induces ATP release from ASM cells. Mechanical stretch was applied to primary human ASM cel...
Source: Am J Respir Cell Mol... - June 2, 2014 Category: Respiratory Medicine Authors: Takahara N, Ito S, Furuya K, Naruse K, Aso H, Kondo M, Sokabe M, Hasegawa Y Tags: Am J Respir Cell Mol Biol Source Type: research