Cyclic stretch induces PlGF expression in bronchial airway epithelial cells via nitric oxide release

2007 ◽  
Vol 292 (2) ◽  
pp. L559-L566 ◽  
Author(s):  
Kamal A. Mohammed ◽  
Najmunnisa Nasreen ◽  
Robert S. Tepper ◽  
Veena B. Antony
Keyword(s):  
Nitric Oxide ◽  
Growth Factors ◽  
Epithelial Cells ◽  
Mechanical Strain ◽  
Airway Epithelial Cells ◽  
Cyclic Stretch ◽  
Mitogen Activated Protein Kinase ◽  
No Production ◽  
Dependent Manner ◽  
Airway Epithelial

Mechanical strain of lung tissue is an important stimulus for the production of growth factors that are critical for lung growth and development. However, excessive mechanical strain, as may occur during mechanical ventilation, may produce an increase in growth factors that may contribute to lung injury. We hypothesized that mechanical strain of primary bronchial airway epithelial cells (BAEpCs) induced the production of placental growth factor (PlGF), a member of the VEGF family. BAEpCs were cultured on a deformable silicoelastic membrane and exposed to different magnitudes of stretch. Stretch induced PlGF and nitric oxide (NO) production that increased with increasing magnitude of stretch. Stretch also induced PlGF and inducible NO synthase ( iNOS) gene expression. The stretch-induced PlGF production and NO synthesis were attenuated by PD98059, a specific mitogen-activated protein kinase kinase-1 and -2 inhibitor. Inhibition of NO generation by l-NAME or l-NMMA or scavenging NO by carboxy-PTIO prevented stretch-mediated erk1/2 activation. In addition, in unstretched BAEpCs, exogenous NO enhanced erk1/erk2 activation. Our data suggest that mechanical stretch of BAEpCs induces iNOS expression and induces PlGF release in an erk1/2 activation-dependent manner.

scholarly journals HSP90 function is required for T2R bitter taste receptor nitric oxide production and innate immune responses in human airway epithelial cells and macrophages

2021 ◽  
Author(s):  
Ryan M Carey ◽  
Benjamin M Hariri ◽  
Nithin D Adappa ◽  
James N Palmer ◽  
Robert J Lee
Keyword(s):  
Nitric Oxide ◽  
Epithelial Cells ◽  
Bitter Taste ◽  
Cell Types ◽  
Airway Epithelial Cells ◽  
Innate Immune ◽  
No Production ◽  
Airway Epithelial ◽  
Primary Monocyte ◽  
Hsp 90

Bitter taste receptors (T2Rs) are G protein-coupled receptors (GPCRs) expressed in various cell types including ciliated airway epithelial cells and macrophages. T2Rs in these two airway innate immune cell types are activated by bitter products, including those secreted by common airway pathogens like Pseudomonas aeruginosa, leading to Ca2+-dependent activation of endothelial nitric oxide (NO) synthase (eNOS). NO production leads to enhanced mucociliary clearance and direct antibacterial effects by ciliated epithelial cells as well as increased phagocytosis by macrophages. Using biochemistry and live cell imaging, we explored the role of heat shock protein 90 (HSP90) in regulating T2R-dependent NO pathways in primary sinonasal epithelial cells, primary monocyte-derived macrophages, and a human bronchiolar cell line (H441). We used immunofluorescence to show that H441 cells express eNOS and certain T2Rs and that the bitterant denatonium benzoate activates NO production in an HSP90-dependent manner in cells grown either as submerged cultures and at air liquid interface. In primary sinonasal epithelial cells, we determined that HSP-90 inhibition reduces T2R-stimulated NO production and ciliary beating which are crucial for pathogen clearance. In primary monocyte-derived macrophages, we found that HSP-90 is integral to T2R-stimulated NO production and phagocytosis of FITC-labeled Escherichia coli and pHrodo-Staphylococcus aureus. Our study demonstrates that HSP90 serves an innate immune role by regulating NO production downstream of T2R signaling by augmenting eNOS activation without impairing upstream calcium signaling. These findings suggest that HSP90 plays an important role in airway antibacterial innate immunity and may be an important target in airway diseases like chronic rhinosinusitis, asthma, or cystic fibrosis.

scholarly journals Osteosarcoma Phenotype Is Inhibited by 3,4-Methylenedioxy-β-nitrostyrene

Sarcoma ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Patrick J. Messerschmitt ◽  
Ashley N. Rettew ◽  
Nicholas O. Schroeder ◽  
Robert E. Brookover ◽  
Avanti P. Jakatdar ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cell Lines ◽  
Colony Formation ◽  
Metastatic Potential ◽  
Airway Epithelial Cells ◽  
Osteosarcoma Cell ◽  
Dependent Manner ◽  
Airway Epithelial ◽  
Human Osteoblasts ◽  
Metastatic Cell Line

β-nitrostyrene compounds, such as 3,4-methylenedioxy-β-nitrostyrene (MNS), inhibit growth and induce apoptosis in tumor cells, but no reports have investigated their role in osteosarcoma. In this study, human osteosarcoma cell families with cell lines of varying tumorigenic and metastatic potential were utilized. Scrape motility assays, colony formation assays, and colony survival assays were performed with osteosarcoma cell lines, both in the presence and absence of MNS. Effects of MNS on human osteoblasts and airway epithelial cells were assessed in monolayer cultures. MNS decreased metastatic cell line motility by 72–76% and colony formation by 95–100%. MNS consistently disrupted preformed colonies in a time-dependent and dose-dependent manner. MNS had similar effects on human osteoblasts but little effect on airway epithelial cells. An inactive analog of MNS had no detectable effects, demonstrating specificity. MNS decreases motility and colony formation of osteosarcoma cells and disrupts preformed cell colonies, while producing little effect on pulmonary epithelial cells.

scholarly journals Mechanical stretch decreases FAK phosphorylation and reduces cell migration through loss of JIP3-induced JNK phosphorylation in airway epithelial cells

2009 ◽  
Vol 297 (3) ◽  
pp. L520-L529 ◽  
Author(s):  
Leena P. Desai ◽  
Steven R. White ◽  
Christopher M. Waters
Keyword(s):  
Cell Migration ◽  
Epithelial Cells ◽  
Mechanical Strain ◽  
Mechanical Stretch ◽  
Inhibitory Effect ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Interacting Protein ◽  
Kinase Activation ◽  
Mapk Cascades

JNK is a nonreceptor kinase involved in the early events that signal cell migration after injury. However, the linkage to early signals required to initiate the migration response to JNK has not been defined in airway epithelial cells, which exist in an environment subjected to cyclic mechanical strain (MS). The present studies demonstrate that the JNK/stress-activated protein kinase-associated protein 1 (JSAP1; also termed JNK-interacting protein 3, JIP3), a scaffold factor for MAPK cascades that links JNK activation to focal adhesion kinase (FAK), are both associated and activated following mechanical injury in 16HBE14o− human airway epithelial cells and that both FAK and JIP3 phosphorylation seen after injury are decreased in cells subjected to cyclic MS. Overexpression of either wild-type (WT)-FAK or WT-JIP3 enhanced phosphorylation and kinase activation of JNK and reduced the inhibitory effect of cyclic MS. These results suggest that cyclic MS impairs signaling of cell migration after injury via a pathway that involves FAK-JIP3-JNK.

scholarly journals Airway epithelial cells prime plasmacytoid dendritic cells to respond to pathogens via secretion of growth factors

2018 ◽  
Vol 12 (1) ◽  
pp. 77-84 ◽  
Author(s):  
Farah Rahmatpanah ◽  
Sudhanshu Agrawal ◽  
Natasha Jaiswal ◽  
Hannah M. Nguyen ◽  
Michael McClelland ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Growth Factors ◽  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Plasmacytoid Dendritic Cells ◽  
Airway Epithelial

A system to impose prescribed homogenous strains on cultured cells

2001 ◽  
Vol 91 (4) ◽  
pp. 1600-1610 ◽  
Author(s):  
Christopher M. Waters ◽  
Matthew R. Glucksberg ◽  
Eugene P. Lautenschlager ◽  
Chyh-Woei Lee ◽  
Reed M. Van Matre ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cultured Cells ◽  
Large Strain ◽  
Mechanical Strain ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Degree Of Anisotropy ◽  
High Degree ◽  
Membrane Shape ◽  
First Time

There is presently significant interest in cellular responses to physical forces, and numerous devices have been developed to apply stretch to cultured cells. Many of the early devices were limited by the heterogeneity of deformation of cells in different locations and by the high degree of anisotropy at a particular location. We have therefore developed a system to impose cyclic, large-strain, homogeneous stretch on a multiwell surface-treated silicone elastomer substrate plated with pulmonary epithelial cells. The pneumatically driven mechanism consists of four plates each with a clamp to fix one edge of the cruciform elastomer substrate. Four linear bearings set at predetermined angles between the plates ensure a constant ratio of principal strains throughout the stretch cycle. We present the design of the device and membrane shape, the surface modifications of the membrane to promote cell adhesion, predicted and experimental measurements of the strain field, and new data using cultured airway epithelial cells. We present for the first time the relationship between the magnitude of cyclic mechanical strain and the extent of wound closure and cell spreading.

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