Cysteinyl leukotrienes enhance growth of human airway epithelial cells

1990 ◽  
Vol 259 (4) ◽  
pp. L255-L261 ◽  
Author(s):  
G. D. Leikauf ◽  
H. E. Claesson ◽  
C. A. Doupnik ◽  
S. Hybbinette ◽  
R. C. Grafstrom
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Epithelial Cell Proliferation ◽  
Leukotriene C4 ◽  
Cysteinyl Leukotrienes ◽  
Human Airway ◽  
Human Airway Epithelial Cells

Epithelial inflammation may play an obligatory role in the pathogenesis of a number of chronic pulmonary diseases such as asthma or bronchitis and has been implicated during the promotion phase of multistage carcinogenesis. At sites of inflammation, bioactive lipid mediators are released and activate a wide range of pathophysiological responses including bronchospasm. Previous studies suggest that one class of inflammatory mediators, the eicosanoids, can also influence cell growth. Epithelial cell proliferation and hyperplasia are common sequelae to irritation and inflammation, and because the lung has a high capacity to produce eicosanoids, we investigated the effects of a group of these compounds, the cysteinyl leukotrienes, on growth of human airway epithelial cells. Leukotrienes were found to be mitogenic in a concentration-dependent manner and exhibit a structure-activity relationship, with leukotriene C4 being more potent than its sequential metabolites leukotriene D4 and E4. The potency of leukotriene C4 is striking, stimulating colony-forming efficiency in concentrations as low as 10 fM. These findings suggest a new physiological role for leukotrienes in the lung that links inflammation with epithelial cell proliferation.

scholarly journals An essential function for autocrine Hedgehog signaling in epithelial proliferation and differentiation in the trachea

2022 ◽  
Author(s):  
Wenguang Yin ◽  
Andreas Liontos ◽  
Janine Koepke ◽  
Maroua Ghoul ◽  
Luciana Mazzocchi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Epithelial Cell Proliferation ◽  
Human Airway ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Hh Signaling

The tracheal epithelium is a primary target for pulmonary diseases as it provides a conduit for air flow between the environment and the lung lobes. The cellular and molecular mechanisms underlying airway epithelial cell proliferation and differentiation remain poorly understood. Hedgehog (Hh) signaling orchestrates communication between epithelial and mesenchymal cells in the lung, where it modulates stromal cell proliferation, differentiation and signaling back to the epithelium. Here, we reveal a new, autocrine function of Hh signaling in airway epithelial cells. Epithelial cell depletion of the ligand Sonic hedgehog (SHH) or its effector Smoothened (SMO) causes defects in both epithelial cell proliferation and differentiation. In cultured primary human airway epithelial cells, Hh signaling inhibition also hampers cell proliferation and differentiation. Epithelial Hh function is mediated, at least in part, through transcriptional activation as Hh signaling inhibition leads to downregulation of cell-type specific transcription factor genes in both the mouse trachea and human airway epithelial cells. These results provide new insights into the role of Hh signaling in epithelial cell proliferation and differentiation during airway development.

scholarly journals Influenza Virus Receptor Specificity and Cell Tropism in Mouse and Human Airway Epithelial Cells

2006 ◽  
Vol 80 (15) ◽  
pp. 7469-7480 ◽  
Author(s):  
Aida Ibricevic ◽  
Andrew Pekosz ◽  
Michael J. Walter ◽  
Celeste Newby ◽  
John T. Battaile ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Airway Epithelial Cell ◽  
Airway Epithelial Cells ◽  
Influenza Viruses ◽  
Mouse Lung ◽  
Airway Epithelial ◽  
Human Airway ◽  
Human Airway Epithelial Cells

ABSTRACT Recent human infections caused by the highly pathogenic avian influenza virus H5N1 strains emphasize an urgent need for assessment of factors that allow viral transmission, replication, and intra-airway spread. Important determinants for virus infection are epithelial cell receptors identified as glycans terminated by an α2,3-linked sialic acid (SA) that preferentially bind avian strains and glycans terminated by an α2,6-linked SA that bind human strains. The mouse is often used as a model for study of influenza viruses, including recent avian strains; however, the selectivity for infection of specific respiratory cell populations is not well described, and any relationship between receptors in the mouse and human lungs is incompletely understood. Here, using in vitro human and mouse airway epithelial cell models and in vivo mouse infection, we found that the α2,3-linked SA receptor was expressed in ciliated airway and type II alveolar epithelial cells and was targeted for cell-specific infection in both species. The α2,6-linked SA receptor was not expressed in the mouse, a factor that may contribute to the inability of some human strains to efficiently infect the mouse lung. In human airway epithelial cells, α2,6-linked SA was expressed and functional in both ciliated and goblet cells, providing expanded cellular tropism. Differences in receptor and cell-specific expression in these species suggest that differentiated human airway epithelial cell cultures may be superior for evaluation of some human strains, while the mouse can provide a model for studying avian strains that preferentially bind only the α2,3-linked SA receptor.

Effect of Adenoviral Vector Infection on Cell Proliferation in Cultured Primary Human Airway Epithelial Cells

1995 ◽  
Vol 6 (8) ◽  
pp. 1045-1053 ◽  
Author(s):  
Shinji Teramoto ◽  
Larry G. Johnson ◽  
Weihong Huang ◽  
Margaret W. Leigh ◽  
Richard C. Boucher
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cells ◽  
Adenoviral Vector ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Human Airway ◽  
Human Airway Epithelial Cells

CXCR3 chemokine receptor-induced chemotaxis in human airway epithelial cells: role of p38 MAPK and PI3K signaling pathways

2006 ◽  
Vol 291 (1) ◽  
pp. C34-C39 ◽  
Author(s):  
Syed Shahabuddin ◽  
Rong Ji ◽  
Ping Wang ◽  
Eugene Brailoiu ◽  
Na Dun ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Signaling Pathways ◽  
P38 Mapk ◽  
Chemokine Receptor ◽  
Airway Epithelial Cells ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Human Airway ◽  
Human Airway Epithelial Cells

Human airway epithelial cells (HAEC) constitutively express the CXC chemokine receptor CXCR3, which regulates epithelial cell movement. In diseases such as chronic obstructive pulmonary disease and asthma, characterized by denudation of the epithelial lining, epithelial cell migration may contribute to airway repair and reconstitution. This study compared the potency and efficacy of three CXCR3 ligands, I-TAC/CXCL11, IP-10/CXCL10, and Mig/CXCL9, as inducers of chemotaxis in HAEC and examined the underlying signaling pathways involved. Studies were performed in cultured HAEC from normal subjects and the 16-HBE cell line. In normal HAEC, the efficacy of I-TAC-induced chemotaxis was 349 ± 88% (mean ± SE) of the medium control and approximately one-half the response to epidermal growth factor, a highly potent chemoattractant. In normal HAEC, Mig, IP-10, and I-TAC induced chemotaxis with similar potency and a rank order of efficacy of I-TAC = IP-10 > Mig. Preincubation with pertussis toxin completely blocked CXCR3-induced migration. Of interest, intracellular [Ca2+] did not rise in response to I-TAC, IP-10, or Mig. I-TAC induced a rapid phosphorylation (5–10 min) of two of the three MAPKs, i.e., p38 and ERK1/2. Pretreatment of HAEC with the p38 inhibitor SB 20358 or the PI3K inhibitor wortmannin dose-dependently inhibited the chemotactic response to I-TAC. In contrast, the ERK1/2 inhibitor U0126 had no effect on chemotaxis. These data indicate that in HAEC, CXCR3-mediated chemotaxis involves a G protein, which activates both the p38 MAPK and PI3K pathways in a calcium-independent fashion.

scholarly journals Comparative primary paediatric nasal epithelial cell culture differentiation and RSV-induced cytopathogenesis following culture in two commercial media

2020 ◽  
Author(s):  
Lindsay Broadbent ◽  
Sheerien Manzoor ◽  
Maria Zarcone ◽  
Judit Barabas ◽  
Mike Shields ◽  
...  
Keyword(s):  
Cell Culture ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Nasal Epithelial Cell ◽  
Human Airway ◽  
Syncytial Virus ◽  
Human Airway Epithelial Cells

AbstractThe culture of differentiated human airway epithelial cells allows the study of pathogen-host interactions and innate immune responses in a physiologically relevant in vitro model. As the use of primary cell culture has gained popularity the availability of the reagents needed to generate these cultures has increased. In this study we assessed two different media, Promocell and PneumaCult, during the differentiation and maintenance of well-differentiated primary nasal epithelial cell cultures (WD-PNECs). We compared and contrasted the consequences of these media on WD-PNEC morphological and physiological characteristics and their responses to respiratory syncytial virus (RSV) infection. We found that cultures generated using PneumaCult resulted in greater total numbers of smaller, tightly packed, pseudostratified cells. However, cultures from both media resulted in similar proportions of ciliated and goblet cells. There were no differences in RSV growth kinetics, although more ciliated cells were infected in the PneumaCult cultures. There was also significantly more IL-29/IFNλ1 secreted from PneumaCult compared to Promocell cultures. In conclusion, the type of medium used for the differentiation of primary human airway epithelial cells impacts experimental results.

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