scholarly journals Induction of nitric oxide release from the human alveolar epithelial cell line A549: an in vitro correlate of innate immune response to Mycobacterium tuberculosis

Immunology ◽  
2004 ◽  
Vol 112 (3) ◽  
pp. 471-480 ◽  
Author(s):  
Sugata Roy ◽  
Sadhna Sharma ◽  
Monika Sharma ◽  
Ramesh Aggarwal ◽  
Mridula Bose
Keyword(s):  
Nitric Oxide ◽  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Alveolar Epithelial Cell ◽  
Innate Immune ◽  
Epithelial Cell Line ◽  
Nitric Oxide Release ◽  
Alveolar Epithelial ◽  
Human Alveolar Epithelial Cell

scholarly journals Transcriptional and Proteomic Characterization of Telomere-Induced Senescence in a Human Alveolar Epithelial Cell Line

2021 ◽  
Vol 8 ◽  
Author(s):  
Daniel I. Sullivan ◽  
Mao Jiang ◽  
Angela M. Hinchie ◽  
Mark G. Roth ◽  
Harinath Bahudhanapati ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Line ◽  
Alveolar Epithelial Cell ◽  
Epithelial Cell Line ◽  
Telomere Dysfunction ◽  
Alveolar Epithelial ◽  
Novel Proteins ◽  
Human Alveolar Epithelial Cell ◽  
Species Specific

Cellular senescence due to telomere dysfunction has been hypothesized to play a role in age-associated diseases including idiopathic pulmonary fibrosis (IPF). It has been postulated that paracrine mediators originating from senescent alveolar epithelia signal to surrounding mesenchymal cells and contribute to disease pathogenesis. However, murine models of telomere-induced alveolar epithelial senescence fail to display the canonical senescence-associated secretory phenotype (SASP) that is observed in senescent human cells. In an effort to understand human-specific responses to telomere dysfunction, we modeled telomere dysfunction-induced senescence in a human alveolar epithelial cell line. We hypothesized that this system would enable us to probe for differences in transcriptional and proteomic senescence pathways in vitro and to identify novel secreted protein (secretome) changes that potentially contribute to the pathogenesis of IPF. Following induction of telomere dysfunction, a robust senescence phenotype was observed. RNA-seq analysis of the senescent cells revealed the SASP and comparisons to previous murine data highlighted differences in response to telomere dysfunction. We conducted a proteomic analysis of the senescent cells using a novel biotin ligase capable of labeling secreted proteins. Candidate biomarkers selected from our transcriptional and secretome data were then evaluated in IPF and control patient plasma. Four novel proteins were found to be differentially expressed between the patient groups: stanniocalcin-1, contactin-1, tenascin C, and total inhibin. Our data show that human telomere-induced, alveolar epithelial senescence results in a transcriptional SASP that is distinct from that seen in analogous murine cells. Our findings suggest that studies in animal models should be carefully validated given the possibility of species-specific responses to telomere dysfunction. We also describe a pragmatic approach for the study of the consequences of telomere-induced alveolar epithelial cell senescence in humans.

scholarly journals Chemokine Production by a Human Alveolar Epithelial Cell Line in Response to Mycobacterium tuberculosis

1998 ◽  
Vol 66 (3) ◽  
pp. 1121-1126 ◽  
Author(s):  
Yuanguang Lin ◽  
Ming Zhang ◽  
Peter F. Barnes
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Epithelial Cell ◽  
Cell Line ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial Cells ◽  
Epithelial Cell Line ◽  
Intracellular Growth ◽  
Chemokine Production ◽  
Alveolar Epithelial ◽  
Human Alveolar Epithelial Cell

ABSTRACT To investigate the role of chemokines during the initial local response to Mycobacterium tuberculosis in the human lung, we studied chemokine production by the human alveolar epithelial cell line A549 after infection with M. tuberculosis. M. tuberculosis-infected A549 cells produced mRNAs and protein for monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) but not mRNAs for macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and RANTES. Chemokine production in response to M. tuberculosis was not dependent on production of tumor necrosis factor alpha, IL-1β, or IL-6. Two virulent clinical M. tuberculosis isolates, the virulent laboratory strain H37Rv, and the avirulent strain H37Ra elicited production of comparable concentrations of MCP-1 and IL-8, whereas killed M. tuberculosis and three Mycobacterium avium strains did not. The three virulent M. tuberculosis strains grew more rapidly than the avirulent M. tuberculosisstrain in the alveolar epithelial cell line, and the threeM. avium strains did not grow intracellularly. These findings suggest that intracellular growth is necessary for mycobacteria to elicit production of MCP-1 and IL-8 by alveolar epithelial cells but that virulence and the rate of intracellular growth do not correlate with chemokine production. Alveolar epithelial cells may contribute to the local inflammatory response in human tuberculosis by producing chemokines which attract monocytes, lymphocytes, and polymorphonuclear cells.

Effect of Steroids on the Synthesis of Complement C3 in a Human Alveolar Epithelial Cell Line

1993 ◽  
Vol 19 (5) ◽  
pp. 603-616 ◽  
Author(s):  
Terence L. Zach ◽  
Vicki A. Herrman ◽  
Laura D. Hill ◽  
M. Patricia Leuschen
Keyword(s):  
Epithelial Cell ◽  
Cell Line ◽  
Alveolar Epithelial Cell ◽  
Complement C3 ◽  
Epithelial Cell Line ◽  
Alveolar Epithelial ◽  
Human Alveolar Epithelial Cell

scholarly journals Consequences of Hypoxia for the Pulmonary Alveolar Epithelial Cell Innate Immune Response

2018 ◽  
Vol 201 (11) ◽  
pp. 3411-3420 ◽  
Author(s):  
Anne Sturrock ◽  
Diana Woller ◽  
Andrew Freeman ◽  
Karl Sanders ◽  
Robert Paine
Keyword(s):  
Immune Response ◽  
Epithelial Cell ◽  
Innate Immune Response ◽  
Alveolar Epithelial Cell ◽  
Innate Immune ◽  
Alveolar Epithelial

scholarly journals GED-0507 attenuates lung fibrosis by counteracting myofibroblast transdifferentiation in vivo and in vitro

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257281
Author(s):  
Silvia Speca ◽  
Caroline Dubuquoy ◽  
Christel Rousseaux ◽  
Philippe Chavatte ◽  
Pierre Desreumaux ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Pulmonary Fibrosis ◽  
Transforming Growth Factor ◽  
Alveolar Epithelial Cell ◽  
Lung Fibroblasts ◽  
Epithelial Cell Line ◽  
Mesenchymal Transition ◽  
Alveolar Epithelial ◽  
Ppar Γ

The development of more effective, better tolerated drug treatments for progressive pulmonary fibrosis (of which idiopathic pulmonary fibrosis is the most common and severe form) is a research priority. The peroxisome proliferator-activated receptor gamma (PPAR-γ) is a key regulator of inflammation and fibrosis and therefore represents a potential therapeutic target. However, the use of synthetic PPAR-γ agonists may be limited by their potentially severe adverse effects. In a mouse model of bleomycin (BLM)-induced pulmonary fibrosis, we have demonstrated that the non-racemic selective PPAR-γ modulator GED-0507 is able to reduce body weight loss, ameliorate clinical and histological features of pulmonary fibrosis, and increase survival rate without any safety concerns. Here, we focused on the biomolecular effects of GED-0507 on various inflammatory/fibrotic pathways. We demonstrated that preventive and therapeutic administration of GED-0507 reduced the BLM-induced mRNA expression of several markers of fibrosis, including transforming growth factor (TGF)-β, alpha-smooth muscle actin, collagen and fibronectin as well as epithelial-to-mesenchymal transition (EMT) and expression of mucin 5B. The beneficial effect of GED-0507 on pulmonary fibrosis was confirmed in vitro by its ability to control TGFβ-induced myofibroblast activation in the A549 human alveolar epithelial cell line, the MRC-5 lung fibroblast line, and primary human lung fibroblasts. Compared with the US Food and Drug Administration-approved antifibrotic drugs pirfenidone and nintedanib, GED-0507 displayed greater antifibrotic activity by controlling alveolar epithelial cell dysfunction, EMT, and extracellular matrix remodeling. In conclusion, GED-0507 demonstrated potent antifibrotic properties and might be a promising drug candidate for the treatment of pulmonary fibrosis.

scholarly journals GM-CSF and the impaired pulmonary innate immune response following hyperoxic stress

2006 ◽  
Vol 291 (6) ◽  
pp. L1246-L1255 ◽  
Author(s):  
Carlos E. O. Baleeiro ◽  
Paul J. Christensen ◽  
Susan B. Morris ◽  
Michael P. Mendez ◽  
Steven E. Wilcoxen ◽  
...  
Keyword(s):  
Immune Response ◽  
Epithelial Cell ◽  
Innate Immune Response ◽  
Alveolar Epithelial Cell ◽  
Critical Role ◽  
Innate Immune ◽  
Alveolar Epithelial Cells ◽  
Bacterial Colony ◽  
Alveolar Epithelial ◽  
Gm Csf

We have previously demonstrated that mice exposed to sublethal hyperoxia (an atmosphere of >95% oxygen for 4 days, followed by return to room air) have significantly impaired pulmonary innate immune response. Alveolar macrophages (AM) from hyperoxia-exposed mice exhibit significantly diminished antimicrobial activity and markedly reduced production of inflammatory cytokines in response to stimulation with LPS compared with AM from control mice in normoxia. As a consequence of these defects, mice exposed to sublethal hyperoxia are more susceptible to lethal pneumonia with Klebsiella pneumoniae than control mice. Granulocyte/macrophage colony-stimulating factor (GM-CSF) is a growth factor produced by normal pulmonary alveolar epithelial cells that is critically involved in maintenance of normal AM function. We now report that sublethal hyperoxia in vivo leads to greatly reduced alveolar epithelial cell GM-CSF expression. Systemic treatment of mice with recombinant murine GM-CSF during hyperoxia exposure preserved AM function, as indicated by cell surface Toll-like receptor 4 expression and by inflammatory cytokine secretion following stimulation with LPS ex vivo. Treatment of hyperoxic mice with GM-CSF significantly reduced lung bacterial burden following intratracheal inoculation with K. pneumoniae, returning lung bacterial colony-forming units to the level of normoxic controls. These data point to a critical role for continuous GM-CSF activity in the lung in maintenance of normal AM function and demonstrate that lung injury due to hyperoxic stress results in significant impairment in pulmonary innate immunity through suppression of alveolar epithelial cell GM-CSF expression.

Sign in / Sign up

Export Citation Format

Share Document