scholarly journals A fungus-derived purpactin A as an inhibitor of TMEM16A chloride channels and mucin secretion in airway epithelial cells

2021 ◽  
Vol 139 ◽  
pp. 111583
Author(s):  
Chantapol Yimnual ◽  
Saravut Satitsri ◽  
Baiq Nila Sari Ningsih ◽  
Vatcharin Rukachaisirikul ◽  
Chatchai Muanprasat
Keyword(s):  
Epithelial Cells ◽  
Chloride Channels ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Mucin Secretion

Carbenoxolone and triterpenoids inhibited mucin secretion from airway epithelial cells

2007 ◽  
Vol 21 (5) ◽  
pp. 462-465 ◽  
Author(s):  
Ho Jin Heo ◽  
Cheolsu Kim ◽  
Hyun Jae Lee ◽  
Young Sik Kim ◽  
Sam Sik Kang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Mucin Secretion

scholarly journals Regulated Mucin Secretion from Airway Epithelial Cells

2013 ◽  
Vol 4 ◽  
Author(s):  
Kenneth B. Adler ◽  
Michael J. Tuvim ◽  
Burton F. Dickey
Keyword(s):  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Mucin Secretion

scholarly journals Inflammation-induced upregulation of P2X4expression augments mucin secretion in airway epithelia

2019 ◽  
Vol 316 (1) ◽  
pp. L58-L70 ◽  
Author(s):  
Veronika E. Winkelmann ◽  
Kristin E. Thompson ◽  
Kathrin Neuland ◽  
Ana M. Jaramillo ◽  
Giorgio Fois ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Defense Mechanism ◽  
Goblet Cells ◽  
Airway Epithelial Cells ◽  
Extracellular Atp ◽  
Airway Epithelial ◽  
Mucin Secretion ◽  
Specific Expression ◽  
Innate Defense

Mucus clearance provides an essential innate defense mechanism to keep the airways and lungs free of particles and pathogens. Baseline and stimulated mucin secretion from secretory airway epithelial cells need to be tightly regulated to prevent mucus hypersecretion and mucus plugging of the airways. It is well established that extracellular ATP is a potent stimulus for regulated mucus secretion. Previous studies revealed that ATP acts via metabotropic P2Y2purinoreceptors on goblet cells. Extracellular ATP, however, is also a potent agonist for ionotropic P2X purinoreceptors. Expression of several P2X isoforms has been reported in airways, but cell type-specific expression and the function thereof remained elusive. With this study, we now provide evidence that P2X4is the predominant P2X isoform expressed in secretory airway epithelial cells. After IL-13 treatment of either human primary tracheal epithelial cells or mice, P2X4expression is upregulated in vitro and in vivo under conditions of chronic inflammation, mucous metaplasia, and hyperplasia. Upregulation of P2X4is strongest in MUC5AC-positive goblet cells. Moreover, activation of P2X4by extracellular ATP augments intracellular Ca2+signals and mucin secretion, whereas Ca2+signals and mucin secretion are dampened by inhibition of P2X4receptors. These data provide new insights into the purinergic regulation of mucin secretion and add to the emerging picture that P2X receptors modulate exocytosis of large secretory organelles and secretion of macromolecular vesicle cargo.

scholarly journals MARCKS and HSP70 interactions regulate mucin secretion by human airway epithelial cells in vitro

2013 ◽  
Vol 304 (8) ◽  
pp. L511-L518 ◽  
Author(s):  
Shijing Fang ◽  
Anne L. Crews ◽  
Wei Chen ◽  
Joungjoa Park ◽  
Qi Yin ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Fluorescent Protein ◽  
Yellow Fluorescent Protein ◽  
Airway Epithelial Cells ◽  
Dependent Manner ◽  
Airway Epithelial ◽  
Mucin Secretion ◽  
Concentration Dependent Manner

Myristoylated alanine-rich C kinase substrate (MARCKS) protein has been recognized as a key regulatory molecule controlling mucin secretion by airway epithelial cells in vitro and in vivo. We recently showed that two intracellular chaperones, heat shock protein 70 (HSP70) and cysteine string protein (CSP), associate with MARCKS in the secretory mechanism. To elucidate more fully MARCKS-HSP70 interactions in this process, studies were performed in well-differentiated normal human bronchial epithelial (NHBE) cells maintained in air-liquid interface culture utilizing specific pharmacological inhibition of HSP70 with pyrimidinone MAL3-101 and siRNA approaches. The results indicate that HSP70 interaction with MARCKS is enhanced after exposure of the cells to the protein kinase C activator/mucin secretagogue, phorbol 12-myristate 13-acetate (PMA). Pretreatment of NHBEs with MAL3-101 attenuated in a concentration-dependent manner PMA-stimulated mucin secretion and interactions among HSP70, MARCKS, and CSP. In additional studies, trafficking of MARCKS in living NHBE cells was investigated after transfecting cells with fluorescently tagged DNA constructs: MARCKS-yellow fluorescent protein, and/or HSP70-cyan fluorescent protein. Cells were treated with PMA 48 h posttransfection, and trafficking of the constructs was examined by confocal microscopy. MARCKS translocated rapidly from plasma membrane to cytoplasm, whereas HSP70 was observed in the cytoplasm and appeared to associate with MARCKS after PMA exposure. Pretreatment of cells with either MAL3-101 or HSP70 siRNA inhibited translocation of MARCKS. These results provide evidence of a role for HSP70 in mediating mucin secretion via interactions with MARCKS and that these interactions are critical for the cytoplasmic translocation of MARCKS upon its phosphorylation.

scholarly journals Ezrin/Exocyst Complex Regulates Mucin 5AC Secretion Induced by Neutrophil Elastase in Human Airway Epithelial Cells

2015 ◽  
Vol 35 (1) ◽  
pp. 326-338 ◽  
Author(s):  
Qi Li ◽  
Na Li ◽  
Chun-Yi Liu ◽  
Rui Xu ◽  
Victor P. Kolosov ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Neutrophil Elastase ◽  
Airway Epithelial Cells ◽  
Specific Marker ◽  
Airway Epithelial ◽  
Mucin Secretion ◽  
Airway Diseases ◽  
Exocyst Complex ◽  
Cell Surface Structures ◽  
Chronic Airway

Background/Aim: Increased mucin secretion is a characteristic feature of many chronic airway diseases, particularly during periods of exacerbation; however, the exact mechanism of mucin secretion remains unclear. Ezrin, which is a specific marker of apical membranes, is predominantly concentrated in exocyst-rich cell surface structures, crosslinking the actin cytoskeleton with the plasma membrane. In the present study, we examined whether Ezrin is involved in mucin 5AC (MUC5AC) secretion after neutrophil elastase (NE) attack, and we investigated the role of the exocyst complex docking protein Sec3 in this process. Methods: NE was used as a stimulator in a 16HBE14o- cell culture model. The expression and location of Ezrin and Sec3 were investigated, and the interaction between Ezrin and Sec3 in 16HBE14o-cells was assayed after treatment with NE, Ezrin siRNA, Sec3 siRNA, neomycin or PIP2-Ab. Results: We found that Ezrin was highly expressed in the bronchi of humans with chronic airway diseases. NE induced robust MUC5AC protein secretion. The Ezrin siRNA, Sec3 siRNA, and neomycin treatments led to impaired MUC5AC secretion in cells. Both Ezrin and Sec3 were recruited primarily to the cytoplasmic membrane after NE stimulation, and the neomycin and PIP2-Ab treatments abrogated this effect. Immunoprecipitation analysis revealed that Ezrin and Sec3 combined to form complexes; however, these complexes could not be detected in Ezrin∆1-333 mutant-transfected cells, even when PIP2 was added. Conclusions: These results demonstrate that Ezrin/Sec3 complexes are essential for MUC5AC secretion in NE-stimulated airway epithelial cells and that PIP2 is of critical importance in the formation of these complexes.

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