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

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Miyamoto, M. (author)

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

Article/chapterEnglish2003

Publisher, publication year, extent ...

2003

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LIBRIS-ID:oai:gup.ub.gu.se/49874
https://gup.ub.gu.se/publication/49874URI

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Language:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Dermatologi och venereologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Dermatology and Venereal Diseases hsv//eng
Administration
Intranasal
Animals
Antibodies
Monoclonal/administration & dosage
Bronchoalveolar Lavage Fluid/cytology/immunology
Dose-Response Relationship
Immunologic
Inflammation/blood/immunology
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

Added entries (persons, corporate bodies, meetings, titles ...)

Prause, O. (author)
Sjöstrand, Margareta,1947Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för lungmedicin och allergologi,Institute of Internal Medicine, Dept of Respiratory Medicine/Allergology(Swepub:gu)xsjosm (author)
Laan, Martti,1971 (author)
Lötvall, Jan,1956Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för lungmedicin och allergologi,Institute of Internal Medicine, Dept of Respiratory Medicine/Allergology(Swepub:gu)xlotja (author)
Lindén, Anders,1961Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för lungmedicin och allergologi,Institute of Internal Medicine, Dept of Respiratory Medicine/Allergology(Swepub:gu)xlandd (author)
Göteborgs universitetInstitutionen för invärtesmedicin, Avdelningen för lungmedicin och allergologi (creator_code:org_t)

Related titles

In:Journal of immunology (Baltimore, Md.170:9, s. 4665-720022-1767

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https://gup.ub.gu.se/publication/49874

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Dermatology and ...

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By the university: University of Gothenburg

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