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*
Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Göteborg University, Gothenburg, Sweden; and
Gene Therapy Core Center, Cardiovascular Research Institute, Department of Laboratory Medicine, University of California, San Francisco, CA 94143.
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-
. 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.
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M. J. Ruddy, F. Shen, J. B. Smith, A. Sharma, and S. L. Gaffen Interleukin-17 regulates expression of the CXC chemokine LIX/CXCL5 in osteoblasts: implications for inflammation and neutrophil recruitment J. Leukoc. Biol., July 1, 2004; 76(1): 135 - 144. [Abstract] [Full Text] [PDF]
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 O Prause, S Bozinovski, G P Anderson, and A Linden Increased matrix metalloproteinase-9 concentration and activity after stimulation with interleukin-17 in mouse airways Thorax, April 1, 2004; 59(4): 313 - 317. [Abstract] [Full Text] [PDF]
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