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Göteborgs universitets publikationer

Endogenous IL-17 as a mediator of neutrophil recruitment caused by endotoxin exposure in mouse airways

Författare och institution:
M. Miyamoto (-); O. Prause (-); Margareta Sjöstrand (Institutionen för invärtesmedicin, Avdelningen för lungmedicin och allergologi); M. Laan (-); Jan Lötvall (Institutionen för invärtesmedicin, Avdelningen för lungmedicin och allergologi); Anders Lindén (Institutionen för invärtesmedicin, Avdelningen för lungmedicin och allergologi)
Publicerad i:
Journal of immunology (Baltimore, Md., 170 ( 9 ) s. 4665-72
0022-1767 (Print)
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
We have previously demonstrated that administration of the recently described cytokine IL-17 in rat airways in vivo recruits and activates neutrophils locally. In the current study, we examined whether endogenous IL-17 is involved in mediating neutrophil recruitment caused by endotoxin exposure in mouse airways. Our in vivo data show that local endotoxin exposure causes the release of free, soluble IL-17 protein 6 h later. Systemic pretreatment with a neutralizing anti-IL-17 Ab almost completely inhibits neutrophil recruitment 24 h, but not 6 h, after endotoxin exposure in the airways. Pretreatment with neutralizing anti-IL-6 and anti-macrophage inflammatory protein (MIP)-2 Abs inhibits neutrophil recruitment caused by local endotoxin exposure and IL-17, respectively. Our in vitro data show that endotoxin exposure stimulates the release of soluble IL-17 protein in T lymphocytes harvested from lung and spleen, respectively, and that this cytokine release requires coculture with airway macrophages. Intracellular IL-17 protein is detected in T lymphocytes from spleen but not in airway macrophages after coculture and stimulation of these two cell types. Finally, anti-IL-17 does not alter endotoxin-induced release of IL-6 and MIP-2 from T lymphocytes and airway macrophages in coculture. In conclusion, our results indicate that endotoxin exposure causes the release of IL-17 from T lymphocytes and that this cytokine release requires the presence of macrophages. Once released, endogenous IL-17 acts in part by inducing local release of neutrophil-mobilizing cytokines such as IL-6 and MIP-2, from nonlymphocyte, nonmacrophage cells, and this contributes to recruitment of neutrophils in the airways. These IL-17-related mechanisms constitute potential targets for pharmacotherapy against exaggerated neutrophil recruitment in airway disease.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Klinisk medicin ->
Dermatologi och venereologi
Administration, Intranasal, Animals, Antibodies, Monoclonal/administration & dosage, Bronchoalveolar Lavage Fluid/cytology/immunology, Dose-Response Relationship, Immunologic, Inflammation/blood/immunology, Inflammation Mediators/analysis/antagonists &, inhibitors/immunology/*physiology, Injections, Intraperitoneal, Interleukin-17/analysis/antagonists & inhibitors/immunology/*physiology, Interleukin-6/antagonists & inhibitors/metabolism/secretion, Lipopolysaccharides/*administration & dosage, Lung/*immunology/pathology, Male, Mice, Mice, Inbred C57BL, Monokines/antagonists & inhibitors/metabolism/secretion, Neutrophil Infiltration/*immunology, Neutrophils/immunology/metabolism/pathology/secretion, Solubility, T-Lymphocytes/immunology/metabolism
Postens nummer:
Posten skapad:
2007-09-25 13:42
Posten ändrad:
2011-01-20 09:59

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