title: A role of GM-CSF in the accumulation of neutrophils in the airways caused by IL-17 and TNF-alpha.
abstract: 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.
authors.affiliation: Lung Pharmacology Group, Dept of Respiratory Medicine and Allergology, Institute of Internal Medicine, Göteborg University, Gothenburg, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Laan
authors.forename: O
authors.initials: O
authors.lastname: Prause
authors.forename: M
authors.initials: M
authors.lastname: Miyamoto
authors.forename: M
authors.initials: M
authors.lastname: Sjöstrand
authors.forename: A M
authors.initials: AM
authors.lastname: Hytönen
authors.forename: T
authors.initials: T
authors.lastname: Kaneko
authors.forename: J
authors.initials: J
authors.lastname: Lötvall
authors.forename: A
authors.initials: A
authors.lastname: Lindén
mesh_terms: D000818:Animals; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002470:Cell Survival; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D015851:Interleukin-7; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor