scholarly journals IL-8 Production in Human Lung Fibroblasts and Epithelial Cells Activated by thePseudomonasAutoinducerN-3-Oxododecanoyl Homoserine Lactone Is Transcriptionally Regulated by NF-κB and Activator Protein-2

2001 ◽  
Vol 167 (1) ◽  
pp. 366-374 ◽  
Author(s):  
Roger S. Smith ◽  
Eric R. Fedyk ◽  
T. A. Springer ◽  
N. Mukaida ◽  
Barbara H. Iglewski ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Human Lung ◽  
Homoserine Lactone ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblasts ◽  
Activator Protein ◽  
Activator Protein 2

ID: 112: ROLE OF PHOSPHOLIPASE D IN IDIOPATHIC PULMONARY FIBROSIS

2016 ◽  
Vol 64 (4) ◽  
pp. 964.1-964
Author(s):  
V Suryadevara ◽  
T Royston ◽  
E Berdyshev ◽  
L Huang ◽  
V Natarajan ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Phospholipase D ◽  
Human Lung ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblasts

Idiopathic pulmonary fibrosis (IPF) is a deadly interstitial disease that leads to scarring and fibrosis of the lung tissue. In pulmonary fibrosis, there is injury and denudation of the alveolar epithelium, which further leads to activation of fibroblasts which differentiate into myofibroblasts. This includes several mechanisms including epithelial to mesenchymal transition (EMT). In this study, we investigated the role of phospholipase D (PLD) in IPF and also its underlying mechanism like EMT and fibroblast proliferation and differentiation. An in vivo murine model of bleomycin-induced pulmonary fibrosis (PF) and in vitro models of murine alveolar type-II epithelial cells (MLE-12) and human lung fibroblasts were used. C57BL/6 and genetically engineered PLD2−/− mice were intratracheally challenged with bleomycin (1.5 U/kg animal) for 14 days and markers of inflammation, EMT and fibrosis were determined. MLE-12 cells were treated with specific PLD1 or PLD2 inhibitors prior to bleomycin (10 mU/ml) challenge, and the role of PLD in EMT and apoptosis of alveolar epithelial cells was studied. Human lung fibroblasts were serum-starved (3h), pretreated with PLD1 or PLD2 inhibitors, and the effect of TGF-β (5 ng/ml) on differentiation of lung fibroblast to myofibroblast was determined. Intra-tracheal instillation of bleomycin in the mice for 14 days leads to the progression of fibrosis in the lung. The lung tissues of the bleomycin treated mice were found to have increased PLD2 protein expression, myofibroblast markers like α-SMA, fibronectin, mesenchymal markers like vimentin, inflammatory cytokines and collagen. Genetic deletion of PLD2 in mice attenuated bleomycin-induced lung inflammation and pulmonary fibrosis. In vitro, MLE-12 cells pretreated with either PLD1 or PLD2 inhibitor did not show a profound reduction either in apoptosis or the expression of transcription factors such as SNAIL, and other markers of EMT. However, MLE-12 cells pretreated with both PLD1 (250 nM) and PLD2 (500 nM) inhibitors were resistant to bleomycin-induced apoptosis, and exhibited reduced expression of SNAIL and mesenchymal markers. On the contrary, human lung fibroblasts pretreated with PLD1 and PLD2 inhibitors showed increased fibroblast to myofibroblast differentiation mediated by TGF-β. The present study suggests a role for PLD2 in bleomycin-induced PF. In vitro, inhibition of both PLD1 and PLD2 was necessary to attenuate bleomycin-induced EMT in epithelial cells and TGF-β mediated differentiation of fibroblasts to myofibroblasts. The in vivo and in vitro results identify the mechanism by which PLD regualtes PF and suggest PLD as a potential therapeutic target in pulmonary fibrosis. This work was supported by National Institutes of Health grant P01 HL98050 to VN.

scholarly journals IL-1α released from damaged epithelial cells is sufficient and essential to trigger inflammatory responses in human lung fibroblasts

2013 ◽  
Vol 7 (3) ◽  
pp. 684-693 ◽  
Author(s):  
M I Suwara ◽  
N J Green ◽  
L A Borthwick ◽  
J Mann ◽  
K D Mayer-Barber ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Human Lung ◽  
Inflammatory Responses ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblasts

scholarly journals A Senescence Bystander Effect in Human Lung Fibroblasts

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1162
Author(s):  
David W. Waters ◽  
Michael Schuliga ◽  
Prabuddha S. Pathinayake ◽  
Lan Wei ◽  
Hui-Ying Tan ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Bystander Effect ◽  
Human Lung ◽  
Primary Cultures ◽  
A549 Cells ◽  
Lung Parenchyma ◽  
Alveolar Epithelial Cells ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblasts

Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterised by a dense fibrosing of the lung parenchyma. An association between IPF and cellular senescence is well established and several studies now describe a higher abundance of senescent fibroblasts and epithelial cells in the lungs of IPF patients compared with age-matched controls. The cause of this abnormal accumulation of senescent cells is unknown but evidence suggests that, once established, senescence can be transferred from senescent to non-senescent cells. In this study, we investigated whether senescent human lung fibroblasts (LFs) and alveolar epithelial cells (AECs) could induce a senescent-like phenotype in “naïve” non-senescent LFs in vitro. Primary cultures of LFs from adult control donors (Ctrl-LFs) with a low baseline of senescence were exposed to conditioned medium (CM) from: (i) Ctrl-LFs induced to become senescent using H2O2 or etoposide; (ii) LFs derived from IPF patients (IPF-LFs) with a high baseline of senescence; or (iii) senescence-induced A549 cells, an AEC line. Additionally, ratios of non-senescent Ctrl-LFs and senescence-induced Ctrl-LFs (100:0, 0:100, 50:50, 90:10, 99:1) were co-cultured and their effect on induction of senescence measured. We demonstrated that exposure of naïve non-senescent Ctrl-LFs to CM from senescence-induced Ctrl-LFs and AECs and IPF-LFs increased the markers of senescence including nuclear localisation of phosphorylated-H2A histone family member X (H2AXγ) and expression of p21, IL-6 and IL-8 in Ctrl-LFs. Additionally, co-cultures of non-senescent and senescence-induced Ctrl-LFs induced a senescent-like phenotype in the non-senescent cells. These data suggest that the phenomenon of “senescence-induced senescence” can occur in vitro in primary cultures of human LFs, and provides a possible explanation for the abnormal abundance of senescent cells in the lungs of IPF patients.

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