Granulocyte colony-stimulating factor blockade enables dexamethasone to inhibit lipopolysaccharide-induced murine lung neutrophils
| Autor: | Mark W. Lingen, Shihong Li, Soon Cheon Shin, Pedro C. Avila, Xin Jiang, Bruce S. Bochner, Nick Z. Lu, Jesus Banuelos, Robert P. Schleimer, Yun Cao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine Neutrophils Physiology medicine.medical_treatment lcsh:Medicine Apoptosis Pathology and Laboratory Medicine Epithelium Dexamethasone White Blood Cells Mice Animal Cells Immune Physiology Granulocyte Colony-Stimulating Factor Medicine and Health Sciences Enzyme-Linked Immunoassays lcsh:Science Immune Response Lung Cells Cultured Innate Immune System Mice Inbred BALB C Multidisciplinary Cell Death Lung Injury respiratory system 3. Good health Cytokine medicine.anatomical_structure Cell Processes Cytokines Tumor necrosis factor alpha Biological Cultures Cellular Types Anatomy medicine.symptom Glucocorticoid Research Article medicine.drug Immune Cells Immunology Inflammation Lung injury Granulocyte Research and Analysis Methods Proinflammatory cytokine 03 medical and health sciences Signs and Symptoms Diagnostic Medicine medicine Animals Humans Immunoassays Glucocorticoids Blood Cells business.industry Macrophages lcsh:R Biology and Life Sciences Epithelial Cells Cell Biology Molecular Development Cell Cultures respiratory tract diseases Biological Tissue 030104 developmental biology Immune System Immunologic Techniques lcsh:Q business Developmental Biology |
| Zdroj: | PLoS ONE, Vol 12, Iss 5, p e0177884 (2017) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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