Neutrophil recruitment by human IL-17 via C-X-C chemokine release in the airways.
IL-17 is a recently discovered cytokine that can be released from activated human CD4+ T lymphocytes. This study assessed the proinflammatory effects of human (h) IL-17 in the airways. In vitro, hIL-17 increased the release of IL-8 in human bronchial epithelial and venous endothelial cells, in a time- and concentration-dependent fashion. This effect of hIL-17 was inhibited by cotreatment with an anti-hIL-17 Ab and was potentiated by hTNF-alpha. In addition, hIL-17 increased the expression of hIL-8 mRNA in bronchial epithelial cells. Conditioned medium from hIL-17-treated bronchial epithelial cells increased human neutrophil migration in vitro. This effect was blocked by an anti-hIL-8 Ab. In vivo, intratracheal instillation of hIL-17 selectively recruited neutrophils into rat airways. This recruitment of neutrophils into the airways was inhibited by an anti-hIL-17 Ab and accompanied by increased levels of rat macrophage inflammatory protein-2 (rMIP-2) in bronchoalveolar lavage (BAL) fluid. The BAL neutrophilia was also blocked by an anti-rMIP-2 Ab. The effect of hIL-17 on the release of hIL-8 and rMIP-2 was also inhibited by glucocorticoids, in vitro and in vivo, respectively. These data demonstrate that hIL-17 can specifically and selectively recruit neutrophils into the airways via the release of C-X-C chemokines from bronchial epithelial cells and suggest a novel mechanism linking the activation of T-lymphocytes to recruitment of neutrophils into the airways.
Laan
M
M
Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Göteborg University, Sweden.
Cui
Z H
ZH
Hoshino
H
H
Lötvall
J
J
Sjöstrand
M
M
Gruenert
D C
DC
Skoogh
B E
BE
Lindén
A
A
D000328:Adult; D000818:Animals; D001980:Bronchi / Q000276:immunology* / Q000378:metabolism*; D002461:Cell Line, Transformed; D019743:Chemokines, CXC / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000502:physiology*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D009504:Neutrophils / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN