Neutrophil recruitment by human IL-17 via CXC chemokine release in the airways

M Laan, ZH Cui, H Hoshino, J Lötvall… - The Journal of …, 1999 - journals.aai.org
M Laan, ZH Cui, H Hoshino, J Lötvall, M Sjöstrand, DC Gruenert, BE Skoogh, A Lindén
The Journal of Immunology, 1999journals.aai.org
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-α. In
addition, hIL-17 increased the expression of hIL-8 mRNA in bronchial epithelial cells …
Abstract
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-α. 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 CXC chemokines from bronchial epithelial cells and suggest a novel mechanism linking the activation of T-lymphocytes to recruitment of neutrophils into the airways.
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