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1 Research Service, Southern Arizona Veterans Health Care System, and Arizona Respiratory Center, University of Arizona, Tucson, Arizona 85723; and 2 The First Department of Internal Medicine and 3 The Second Department of Surgery, School of Medicine, Shinshu University, Matsumoto, Japan 390-0802
Chemotactic chemokines can
be released from lung fibroblasts in response to interleukin (IL)-1
and tumor necrosis factor (TNF)-
. An imbalance between proteases and
antiproteases has been observed at inflammatory sites, and, therefore,
protease inhibitors might modulate fibroblast release of chemotactic
cytokines. To test this hypothesis, serine protease inhibitors (FK-706,
1-antitrypsin, or
N
-p-tosyl-L-lysine chloromethyl
ketone) were evaluated for their capacity to attenuate the release of
neutrophil chemotactic activity (NCA) or monocyte chemotactic activity
(MCA) from human fetal lung fibroblasts (HFL-1). Similarly, the release
of the chemoattractants IL-8, granulocyte colony-stimulating factor, monocyte chemoattractant protein-1, macrophage colony-stimulating factor, and granulocyte/macrophage colony-stimulating factor, from
HFL-1, were evaluated in response to IL-1
and TNF-
. NCA, MCA, and
chemotactic cytokines were attenuated by FK-706. However, matrix
metalloproteinase inhibitors were without effect, and cysteine protease
inhibitors only slightly attenuated chemotactic or cytokine release.
These data suggest that IL-1
and TNF-
may stimulate lung
fibroblasts to release NCA and MCA by a protease-dependent mechanism
and that serine protease inhibitors may attenuate the release.
neutrophil; monocyte; interleukin-8; monocyte chemoattractant protein-1; granulocyte/macrophage colony- stimulating factor
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