Glucocorticoid regulation of GM-CSF: evidence for transcriptional mechanisms in airway epithelial cells

1998 ◽  
Vol 275 (2) ◽  
pp. L372-L378 ◽  
Author(s):  
Karissa K. Adkins ◽  
Tricia D. Levan ◽  
Roger L. Miesfeld ◽  
John W. Bloom
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Cell Line ◽  
Bronchial Epithelial Cell ◽  
Airway Epithelial Cells ◽  
Epithelial Cell Line ◽  
Airway Epithelial ◽  
Dexamethasone Treatment ◽  
Bronchial Epithelial ◽  
Gm Csf

Inflammation plays a central role in the pathogenesis of asthma. Glucocorticoids are first-line anti-inflammatory therapy in the treatment of asthma and are effective inhibitors of inflammatory cytokines. Clinical data demonstrate that granulocyte-macrophage colony-stimulating factor (GM-CSF) production by airway epithelial cells may be an important target of inhaled glucocorticoid therapy. We examined the regulatory mechanisms of GM-CSF expression by interleukin-1β (IL-1β) and the synthetic glucocorticoid dexamethasone in the BEAS-2B human bronchial epithelial cell line. IL-1β stimulation resulted in a 15-fold induction of GM-CSF protein, which was associated with a corresponding 47-fold maximal induction of GM-CSF mRNA levels. Treatment with the transcriptional inhibitor actinomycin D before IL-1β stimulation completely abolished induction of GM-CSF mRNA, whereas incubation with cycloheximide had no effect. Taken together, these data demonstrate that IL-1β induction of GM-CSF is mediated through transcriptional mechanisms. Dexamethasone treatment of BEAS-2B cells produced an 80% inhibition of IL-1β-induced GM-CSF protein and a 51% inhibition of GM-CSF mRNA. GM-CSF mRNA was rapidly degraded in these cells, and dexamethasone treatment did not significantly affect this decay rate. We conclude that, in the BEAS-2B bronchial epithelial cell line, IL-1β induction and dexamethasone repression of GM-CSF expression are mediated predominantly through transcriptional mechanisms.

Signaling intermediates required for NF-κB activation and IL-8 expression in CF bronchial epithelial cells

2003 ◽  
Vol 284 (2) ◽  
pp. L307-L315 ◽  
Author(s):  
Jing Li ◽  
Xa Dwight Johnson ◽  
Svetlana Iazvovskaia ◽  
Alan Tan ◽  
Anning Lin ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cell Line ◽  
Bronchial Epithelial Cell ◽  
Airway Epithelial Cells ◽  
Epithelial Cell Line ◽  
Airway Epithelial ◽  
Independent Manner ◽  
Bronchial Epithelial ◽  
Erk Activation ◽  
Iκb Kinase

Ligation of the asialoGM1 Pseudomonas aeruginosa pilin receptor has been demonstrated to induce IL-8 expression in airway epithelial cells via an NF-κB-dependent pathway. We examined the signaling pathways required for asialoGM1-mediated NF-κB activation in IB3 cells, a human bronchial epithelial cell line derived from a cystic fibrosis (CF) patient, and C-38 cells, the rescued cell line that expresses a functional CF transmembrane regulator. Ligation of the asialoGM1 receptor with specific antibody induced greater IL-8 expression in IB3 cells than C-38 cells, consistent with the greater density of asialoGM1 receptors in CF phenotype cells. AsialoGM1-mediated activation of NF-κB, IκB kinase (IKK), and ERK was also greater in IB3 cells. With the use of genetic inhibitors, we found that IKK-β and NF-κB-inducing kinase are required for maximal NF-κB transactivation and transcription from the IL-8 promoter. Finally, although ERK activation was required for maximal asialoGM1-mediated IL-8 expression, inhibition of ERK signaling had no effect on IKK or NF-κB activation, suggesting that ERK regulates IL-8 expression in an NF-κB-independent manner.

scholarly journals Expression/Activation of PAR-1 in Airway Epithelial Cells of COPD Patients: Ex Vivo/In Vitro Study

2021 ◽  
Vol 22 (19) ◽  
pp. 10703
Author(s):  
Angela Marina Montalbano ◽  
Giuseppina Chiappara ◽  
Giusy Daniela Albano ◽  
Maria Ferraro ◽  
Caterina Di Sano ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Ex Vivo ◽  
In Vitro Study ◽  
Bronchial Epithelial Cell ◽  
Airway Epithelial Cells ◽  
Epithelial Cell Line ◽  
Airway Epithelial ◽  
Bronchial Epithelial ◽  
Copd Patients

The role of PAR-1 expression and activation was described in epithelial cells from the central and distal airways of COPD patients using an ex vivo/in vitro model. PAR-1 immunoreactivity was studied in epithelial cells from surgical specimens of the central and distal airways of COPD patients and healthy control (HC). Furthermore, PAR-1 expression and activation were measured in both the human bronchial epithelial cell line (16HBE) and normal human bronchial epithelial cells (NHBEs) exposed to cigarette smoke extract (CSE) (10%) or thrombin. Finally, cell proliferation, apoptosis, and IL-8 release were detected in stimulated NHBEs. We identified higher levels of PAR-1 expression/activation in epithelial cells from the central airways of COPD patients than in HC. Active PAR-1 increased in epithelial cells from central and distal airways of COPD, with higher levels in COPD smokers (correlated with pack-years) than in COPD ex-smokers. 16HBE and NHBEs exposed to CSE or thrombin showed increased levels of active PAR-1 (localized in the cytoplasm) than baseline conditions, while NHBEs treated with thrombin or CSE showed increased levels of IL-8 proteins, with an additional effect when used in combination. Smoking habits generate the upregulation of PAR-1 expression/activation in airway epithelial cells, and promoting IL-8 release might affect the recruitment of infiltrating cells in the airways of COPD patients.

Corticosteroids differentially regulate secretion of IL-6, IL-8, and G-CSF by a human bronchial epithelial cell line

1993 ◽  
Vol 265 (4) ◽  
pp. L360-L368 ◽  
Author(s):  
S. J. Levine ◽  
P. Larivee ◽  
C. Logun ◽  
C. W. Angus ◽  
J. H. Shelhamer
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Cell Line ◽  
Bronchial Epithelial Cell ◽  
Bronchial Epithelial Cells ◽  
Human Bronchial Epithelial Cell ◽  
Tnf Alpha ◽  
Epithelial Cell Line ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial

Human airway epithelial cells play an active role in modulating airway inflammation by elaborating a variety of proinflammatory molecules, including cytokines. The purpose of this study was to define the role of corticosteroids in the regulation of cytokine gene transcription and secretion by human bronchial epithelial cells. In particular, we assessed whether dexamethasone was capable of inhibiting the tumor necrosis factor-alpha (TNF-alpha)-mediated secretion of interleukin-6 (IL-6), interleukin-8 (IL-8), and granulocyte colony-stimulating factor (G-CSF) by a human bronchial epithelial cell line (BEAS-2B). Stimulation with 20 ng/ml of TNF-alpha resulted in significant increases in secretion of immunoreactive IL-6, IL-8, and G-CSF that were maximal at 24 h. TNF-alpha-mediated IL-6, IL-8, and G-CSF secretion was concentration dependent and specific. In addition, stimulation with TNF-alpha resulted in significant increases in the quantity of IL-6, IL-8, and G-CSF mRNA as detected by reverse-transcription polymerase chain reaction. Dexamethasone preconditioning significantly inhibited both the secretion of immunoreactive IL-6 and the accumulation of IL-6 mRNA. Although dexamethasone appeared to reduce both the secretion of immunoreactive IL-8 and accumulation of IL-8 mRNA, the inhibitory effects did not reach statistical significance. Finally, dexamethasone did not inhibit either the secretion of immunoreactive G-CSF or the accumulation of G-CSF mRNA. In summary, our results suggest that corticosteroids have a differential effect on the regulation of cytokine secretion by human bronchial epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Biosynthesized matrix provides a key role for survival signaling in bronchial epithelial cells

2004 ◽  
Vol 286 (3) ◽  
pp. L596-L603 ◽  
Author(s):  
Sam J. Wadsworth ◽  
Anette M. Freyer ◽  
Randolph L. Corteling ◽  
Ian P. Hall
Keyword(s):  
Growth Factors ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Cell Survival ◽  
Cell Line ◽  
Bronchial Epithelial Cell ◽  
Bronchial Epithelial Cells ◽  
Epithelial Cell Line ◽  
Bronchial Epithelial ◽  
Survival Signals

The extracellular matrix (ECM) influences a variety of cellular functions, including survival, adhesion molecule expression, differentiation, and migration. The ECM composition of the epithelial basement membrane is altered in asthmatics. In this study, we elucidate the major survival signals received by bronchial epithelial cells in vitro by studying the effects of a variety of ECM factors and soluble growth factors on bronchial epithelial cell survival. Our findings indicate that the insulin family of soluble growth factors provides important survival signals but also that adhesion to ECM is a crucial determinant of bronchial epithelial cell survival. In the BEAS-2B bronchial epithelial cell line, collagens I and IV, laminin, fibronectin, and vitronectin provide significant levels of protection from apoptosis. Tenascin-C has no effect, whereas elastin and collagen V increase apoptosis to above control levels. BEAS-2B cells secrete their own biosynthesized matrix (BSM), which also provides rescue from apoptosis. Protection by collagen I, fibronectin, and vitronectin was found to be via an RGD domain. Laminin-, collagen IV-, and BSM-mediated survival is not RGD dependent. Primary bronchial epithelial cells exhibit a similar pattern of apoptosis rescue to the BEAS-2B cell line, although we did not observe any vitronectin-mediated protection in the primary cells. These data indicate that bronchial epithelial cell survival is dependent both on soluble growth factors and on a variety of ECM-derived signals.

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