Role of claudin interactions in airway tight junctional permeability

2003 ◽  
Vol 285 (5) ◽  
pp. L1166-L1178 ◽  
Author(s):  
Carolyn B. Coyne ◽  
Todd M. Gambling ◽  
Richard C. Boucher ◽  
Johnny L. Carson ◽  
Larry G. Johnson
Keyword(s):  
Cell Lines ◽  
Airway Epithelium ◽  
Airway Epithelial ◽  
Solute Permeability ◽  
Human Airway ◽  
Human Airway Epithelium ◽  
Junctional Permeability ◽  
Human Airways ◽  
Nih 3T3

Airway epithelial tight junctions (TJs) serve to separate the external and internal environments of the lung. However, the members of the claudin family that mediate this function have not been fully delineated. We characterized the claudin expression in normal airways removed from human donors during lung transplantation and determined the contribution of each claudin to airway barrier function. Stable cell lines in NIH/3T3 and human airway (IB3.1) cells were constructed expressing the claudin components found in the human airway, claudin-1, -3, or -5. The effects of claudin expression on transepithelial resistance, permeability coefficients, and claudin-claudin interactions were assessed. Claudin-1 and -3 decreased solute permeability, whereas claudin-5 increased permeability. We also detected oligomerization of claudin-5 in cell lines and in freshly excised human airways. Coimmunoprecipitation studies revealed heterophilic interactions between claudin species in both cell lines and human airway epithelium. These suggest that airway TJs are regulated by claudinclaudin interactions that confer the selectivity of the junction.

scholarly journals Somatic cell hemoglobin modulates nitrogen oxide metabolism in the human airway epithelium

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nadzeya Marozkina ◽  
Laura Smith ◽  
Yi Zhao ◽  
Joe Zein ◽  
James F. Chmiel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Nitrogen Oxides ◽  
Airway Epithelium ◽  
Airflow Obstruction ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Human Airway ◽  
Human Airway Epithelium ◽  
Human Airway Epithelial Cells

AbstractEndothelial hemoglobin (Hb)α regulates endothelial nitric oxide synthase (eNOS) biochemistry. We hypothesized that Hb could also be expressed and biochemically active in the ciliated human airway epithelium. Primary human airway epithelial cells, cultured at air–liquid interface (ALI), were obtained by clinical airway brushings or from explanted lungs. Human airway Hb mRNA data were from publically available databases; or from RT-PCR. Hb proteins were identified by immunoprecipitation, immunoblot, immunohistochemistry, immunofluorescence and liquid chromatography- mass spectrometry. Viral vectors were used to alter Hbβ expression. Heme and nitrogen oxides were measured colorimetrically. Hb mRNA was expressed in human ciliated epithelial cells. Heme proteins (Hbα, β, and δ) were detected in ALI cultures by several methods. Higher levels of airway epithelial Hbβ gene expression were associated with lower FEV1 in asthma. Both Hbβ knockdown and overexpression affected cell morphology. Hbβ and eNOS were apically colocalized. Binding heme with CO decreased extracellular accumulation of nitrogen oxides. Human airway epithelial cells express Hb. Higher levels of Hbβ gene expression were associated with airflow obstruction. Hbβ and eNOS were colocalized in ciliated cells, and heme affected oxidation of the NOS product. Epithelial Hb expression may be relevant to human airways diseases.

scholarly journals Role of OSGIN1 in mediating smoking-induced autophagy in the human airway epithelium

Autophagy ◽  
2017 ◽  
Vol 13 (7) ◽  
pp. 1205-1220 ◽  
Author(s):  
Guoqing Wang ◽  
Haixia Zhou ◽  
Yael Strulovici-Barel ◽  
Mohammed Al-Hijji ◽  
Xuemei Ou ◽  
...  
Keyword(s):  
Airway Epithelium ◽  
Human Airway ◽  
Human Airway Epithelium

Role Of MiRNA Let-7c In Modulating Differentiation Of Human Airway Epithelium

2012 ◽  
Author(s):  
Rui Wang ◽  
Guoqing Wang ◽  
Jacqueline Salit ◽  
Joumana Ahmed ◽  
Ronald G. Crystal
Keyword(s):  
Airway Epithelium ◽  
Human Airway ◽  
Human Airway Epithelium

scholarly journals Long-term Reconstruction of Human Airway Epithelium-like Structure in Vivo with hESCs-derived organoid cells

2020 ◽  
Author(s):  
Yong Chen ◽  
Le Han ◽  
Shanshan Zhao ◽  
Jianqi Feng ◽  
Lian Li ◽  
...  
Keyword(s):  
Airway Epithelium ◽  
Lung Development ◽  
Embryonic Stem ◽  
Airway Epithelial ◽  
Human Airway ◽  
Human Airway Epithelium ◽  
Nsg Mice ◽  
Pseudostratified Epithelium

AbstractHuman embryonic stem cells (hESCs) derived lung organoids (HLOs) provide a promising model to study human lung development and disease. However, whether HLO cells could reconstitute airway epithelial structure in vivo remains unclear. Here we established an orthotopic xenograft system for hESCs-derived HLOs, enabling stable reconstruction of human airway epithelium in vivo. Removal of the mouse airway epithelium by naphthalene (NA) treatment enabled xenografted organoid cells survival, differentiation, and reconstruction of airway pseudostratified epithelium in immune-compromised NSG mice. Compared to unsorted pool cells, CD47high cells generated more ciliated cells and possessed thicker pseudostratified epithelium. RNA-seq data revealed that CD47high cells highly expressed epithelial cell, lung progenitor, lung proximal cell and embryonic lung development associated genes. These data reveal that HLOs hold cell therapy potential in regenerative medicine by long-term reconstituting airway epithelium.

scholarly journals JAK inhibitors dampen activation of interferon-stimulated transcription of ACE2 isoforms in human airway epithelial cells

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Hye Kyung Lee ◽  
Olive Jung ◽  
Lothar Hennighausen
Keyword(s):  
Airway Epithelium ◽  
Airway Epithelial Cells ◽  
Janus Kinase ◽  
Cell Tropism ◽  
Airway Epithelial ◽  
Rna Seq ◽  
Jak Inhibitors ◽  
Angiotensin Converting Enzyme 2 ◽  
Human Airway ◽  
Human Airway Epithelium

AbstractSARS-CoV-2 infection of human airway epithelium activates genetic programs leading to progressive hyperinflammation in COVID-19 patients. Here, we report on transcriptomes activated in primary airway cells by interferons and their suppression by Janus kinase (JAK) inhibitors. Deciphering the regulation of the angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2, is paramount for understanding the cell tropism of SARS-CoV-2 infection. ChIP-seq for activating histone marks and Pol II loading identified candidate enhancer elements controlling the ACE2 locus, including the intronic dACE2 promoter. Employing RNA-seq, we demonstrate that interferons activate expression of dACE2 and, to a lesser extent, the genuine ACE2 gene. Interferon-induced gene expression was mitigated by the JAK inhibitors baricitinib and ruxolitinib, used therapeutically in COVID-19 patients. Through integrating RNA-seq and ChIP-seq data we provide an in-depth understanding of genetic programs activated by interferons, and our study highlights JAK inhibitors as suitable tools to suppress these in bronchial cells.

scholarly journals The FOXA1 transcriptional network coordinates key functions of primary human airway epithelial cells

2020 ◽  
Vol 319 (1) ◽  
pp. L126-L136
Author(s):  
Alekh Paranjapye ◽  
Michael J. Mutolo ◽  
Jey Sabith Ebron ◽  
Shih-Hsing Leir ◽  
Ann Harris
Keyword(s):  
Transcription Factors ◽  
Epithelial Cells ◽  
Airway Epithelium ◽  
Epithelial To Mesenchymal Transition ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Mesenchymal Transition ◽  
Human Airway ◽  
Human Airway Epithelium ◽  
Two Factors

The differentiated functions of the human airway epithelium are coordinated by a complex network of transcription factors. These include the pioneer factors Forkhead box A1 and A2 (FOXA1 and FOXA2), which are well studied in several tissues, but their role in airway epithelial cells is poorly characterized. Here, we define the cistrome of FOXA1 and FOXA2 in primary human bronchial epithelial (HBE) cells by chromatin immunoprecipitation with deep-sequencing (ChIP-seq). Next, siRNA-mediated depletion of each factor is used to investigate their transcriptome by RNA-seq. We found that, as predicted from their DNA-binding motifs, genome-wide occupancy of the two factors showed substantial overlap; however, their global impact on gene expression differed. FOXA1 is an abundant transcript in HBE cells, while FOXA2 is expressed at low levels, and both these factors likely exhibit autoregulation and cross-regulation. FOXA1 regulated loci are involved in cell adhesion and the maintenance of epithelial cell identity, particularly through repression of genes associated with epithelial to mesenchymal transition (EMT). FOXA1 also directly targets other transcription factors with a known role in the airway epithelium such as SAM-pointed domain-containing Ets-like factor (SPDEF). The intersection of the cistrome and transcriptome for FOXA1 revealed enrichment of genes involved in epithelial development and tissue morphogenesis. Moreover, depletion of FOXA1 was shown to reduce the transepithelial resistance of HBE cells, confirming the role of this factor in maintaining epithelial barrier integrity.

scholarly journals Investigation of the role of the autophagic protein LC3B in the regulation of human airway epithelium cell differentiation in COPD using a biomimetic model

2022 ◽  
Vol 13 ◽  
pp. 100182
Author(s):  
Shiue-Luen Chen ◽  
Hsiao-Chun Chou ◽  
Kuan-Chen Lin ◽  
Jia-Wei Yang ◽  
Ren-Hao Xie ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Airway Epithelium ◽  
Human Airway ◽  
Human Airway Epithelium ◽  
Epithelium Cell

scholarly journals Glycated Albumin Triggers an Inflammatory Response in the Human Airway Epithelium and Causes an Increase in Ciliary Beat Frequency

2021 ◽  
Vol 12 ◽  
Author(s):  
Moira L. Aitken ◽  
Ranjani Somayaji ◽  
Thomas R. Hinds ◽  
Maricela Pier ◽  
Karla Droguett ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Epithelium ◽  
Glycated Albumin ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Human Airway ◽  
Human Airway Epithelium ◽  
Ciliary Beat

The role of inflammation in airway epithelial cells and its regulation are important in several respiratory diseases. When disease is present, the barrier between the pulmonary circulation and the airway epithelium is damaged, allowing serum proteins to enter the airways. We identified that human glycated albumin (GA) is a molecule in human serum that triggers an inflammatory response in human airway epithelial cultures. We observed that single-donor human serum induced IL-8 secretion from primary human airway epithelial cells and from a cystic fibrosis airway cell line (CF1-16) in a dose-dependent manner. IL-8 secretion from airway epithelial cells was time dependent and rapidly increased in the first 4 h of incubation. Stimulation with GA promoted epithelial cells to secrete IL-8, and this increase was blocked by the anti-GA antibody. The IL-8 secretion induced by serum GA was 10–50-fold more potent than TNFα or LPS stimulation. GA also has a functional effect on airway epithelial cells in vitro, increasing ciliary beat frequency. Our results demonstrate that the serum molecule GA is pro-inflammatory and triggers host defense responses including increases in IL-8 secretion and ciliary beat frequency in the human airway epithelium. Although the binding site of GA has not yet been described, it is possible that GA could bind to the receptor for advanced glycated end products (RAGE), known to be expressed in the airway epithelium; however, further experiments are needed to identify the mechanism involved. We highlight a possible role for GA in airway inflammation.

Alpha-adrenergic regulation of Na-Cl cotransport in human airway epithelium

1989 ◽  
Vol 257 (2) ◽  
pp. L125-L129 ◽  
Author(s):  
C. M. Liedtke
Keyword(s):  
Epithelial Cells ◽  
Airway Epithelium ◽  
Initial Rate ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Adrenergic Agonist ◽  
Beta Adrenergic ◽  
Human Airway ◽  
Cl Transport ◽  
Human Airway Epithelium

The demonstration of abnormal beta-adrenergic and cAMP-modulated apical Cl- channels in cystic fibrosis (CF) airway epithelial cells suggests that other transporters, which are required for Cl- secretion, may also be abnormally regulated. A basolateral cotransporter was investigated by determining the initial rate of 36Cl efflux from cells isolated from CF nasal polyps or trachea and non-CF trachea. Cells were preequilibrated with radioactive tracer at 25 degrees C, and tracer transport was initiated by 10-fold dilution of an aliquot of cells in radioisotope-free medium. The initial rate of Cl transport was calculated from the linear portion of the efflux curves. In CF and non-CF cells, base-line Cl- transport was not blocked by furosemide but was stimulated twofold by l-epinephrine in Ca2+-deficient and Ca2+-replete transport medium. In both types of cells, furosemide blocked 70 and 77%, respectively, of the stimulated Cl- transport. Prazosin, an alpha 1-adrenergic antagonist, blocked the effects of l-epinephrine and methoxamine, an alpha 1-adrenergic agonist, stimulated prazosin- and furosemide-sensitive Cl transport. Ionomycin mimicked the effects of l-epinephrine. l-Isoproterenol, a beta-adrenergic agonist, did not affect Cl transport. The results of this study indicate an alpha 1-adrenergic stimulation of furosemide-sensitive Cl transport in human airway epithelium that functions normally in CF airway epithelial cells. The transport mechanism is probably a Na-Cl or Na-K-2Cl cotransport located in the basolateral membrane and requires elevated intracellular Ca2+ for activation.

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