Granulocyte colony-stimulating factor blockade enables dexamethasone to inhibit lipopolysaccharide-induced murine lung neutrophils

Jesus Banuelos, Yun Cao, Soon Cheon Shin, Bruce Scott Bochner, Pedro Avila, Shihong Li, Xin Jiang, Mark W. Lingen, Robert P Schleimer, Nick Z. Lu

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Glucocorticoids promote neutrophilic inflammation, the mechanisms of which are poorly characterized. Using a lipopolysaccharide (LPS)-induced acute murine lung injury model, we determined the role of granulocyte colony-stimulating factor (G-CSF) in mouse lung neutrophil numbers in the absence and presence of dexamethasone, a potent glucocorticoid. G-CSF was blocked using a neutralizing antibody. Airway neutrophil numbers, cytokine levels, and lung injury parameters were measured. Glucocorticoid treatment maintained LPS-induced airway G-CSF while suppressing TNF and IL-6. The addition of anti-G-CSF antibodies enabled dexamethasone to decrease airway G-CSF, neutrophils, and lung injury scores. In LPS-challenged murine lungs, structural cells and infiltrating leukocytes produced G-CSF. In vitro using BEAS 2B bronchial epithelial cells, A549 lung epithelial cells, human monocyte-derived macrophages, and human neutrophils, we found that dexamethasone and proinflammatory cytokines synergistically induced G-CSF. Blocking G-CSF production in BEAS 2B cells using shRNAs diminished the ability of BEAS 2B cells to protect neutrophils from undergoing spontaneous apoptosis. These data support that G-CSF plays a role in upregulation of airway neutrophil numbers by dexamethasone in the LPS-induced acute lung injury model.

Original languageEnglish (US)
Article numbere0177884
JournalPloS one
Volume12
Issue number5
DOIs
StatePublished - May 1 2017

Fingerprint

granulocyte colony-stimulating factor
Granulocyte Colony-Stimulating Factor
dexamethasone
lipopolysaccharides
Dexamethasone
Lipopolysaccharides
neutrophils
Neutrophils
lungs
Lung
mice
glucocorticoids
Glucocorticoids
Acute Lung Injury
Lung Injury
epithelial cells
cytokines
Epithelial Cells
Cytokines
Macrophages

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Banuelos, Jesus ; Cao, Yun ; Shin, Soon Cheon ; Bochner, Bruce Scott ; Avila, Pedro ; Li, Shihong ; Jiang, Xin ; Lingen, Mark W. ; Schleimer, Robert P ; Lu, Nick Z. / Granulocyte colony-stimulating factor blockade enables dexamethasone to inhibit lipopolysaccharide-induced murine lung neutrophils. In: PloS one. 2017 ; Vol. 12, No. 5.
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Granulocyte colony-stimulating factor blockade enables dexamethasone to inhibit lipopolysaccharide-induced murine lung neutrophils. / Banuelos, Jesus; Cao, Yun; Shin, Soon Cheon; Bochner, Bruce Scott; Avila, Pedro; Li, Shihong; Jiang, Xin; Lingen, Mark W.; Schleimer, Robert P; Lu, Nick Z.

In: PloS one, Vol. 12, No. 5, e0177884, 01.05.2017.

Research output: Contribution to journalArticle

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