A role of GM-CSF in the accumulation of neutrophils in the airways caused by IL-17 and TNF-alpha

• The T-cell cytokine interleukin (IL)-17 selectively accumulates neutrophils in murine airways in vivo and may thus constitute a link between activation of T-lymphocytes and accumulation of neutrophils. In this study, the authors evaluated the role of granulocyte macrophage-colony stimulating factor (GM-CSF) in accumulation of neutrophils in the airways caused by IL-17 and tumour necrosis factor (TNF)-alpha. In vitro, human (h) IL-17 concentration-dependently stimulated the release of GM-CSF protein (enzyme-linked immunosorbent assay) in human bronchial epithelial cells (16HBE). IL-17 also time-dependently stimulated the release of GM-CSF protein in venous endothelial (human umbilical vein endothelial cells) cells in vitro. Co-stimulation with IL-17 plus the pro-inflammatory cytokine TNF-alpha potentiated the release of GM-CSF protein in 16HBE cells. hIL-17 also enhanced the expression of GM-CSF messenger ribonucleic acid in 16HBE cells (reverse transcriptase polymerase chain reaction), with a similar order of magnitude as TNF-alpha. Conditioned cell medium from bronchial epithelial cells co-stimulated with hIL-17 plus TNF-alpha prolonged survival (trypan blue exclusion) of human neutrophils in vitro and this effect was blocked by an anti-GM-CSF antibody. In vivo, local co-stimulation with mouse IL-17 plus TNF-alpha caused an additive potentiation of the accumulation of neutrophils in bronchoalveolar lavage fluid from mouse airways and this effect was blocked by an anti-GM-CSF antibody given systemically. In conclusion, granulocyte macrophage-colony stimulating factor is involved in the accumulation of neutrophils in the airways caused by interleukin-17 and tumour necrosis factor-alpha, probably via effects on both recruitment and survival of neutrophils.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

Animals

Bronchial Hyperreactivity/physiopathology

Bronchoalveolar Lavage Fluid/cytology

Cell Survival

Cells

Cultured

Disease Models

Animal

Dose-Response Relationship

Drug

Granulocyte-Macrophage Colony-Stimulating Factor/analysis/*metabolism

Humans

Interleukin-7/*pharmacology

Lymphocyte Activation/drug effects/physiology

Male

Mice

Mice

Inbred C57BL

Neutrophil Activation/*drug effects

Neutrophils/*drug effects/physiology

Probability

RNA

Messenger/analysis/drug effects

Sensitivity and Specificity

Statistics

Nonparametric

Tumor Necrosis Factor-alpha/*pharmacology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)