Serine protease inhibitors modulate chemotactic cytokine production by human lung fibroblasts in vitro

• Published in: American journal of physiology. Lung cellular and molecular physiology 2003-05, Vol.284 (5), p.882-L890
• Main Authors: Numanami, Hiroki, Koyama, Sekiya, Sato, Esturo, Haniuda, Masayuki, Nelson, Dan K, Hoyt, Jeffrey C, Freels, Jon L, Habib, Michael P, Robbins, Richard A
• Format: Article
• Language: English
• Subjects: alpha 1-Antitrypsin - pharmacology; Antineoplastic Agents - pharmacology; Benzoates - pharmacology; Cells, Cultured; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - metabolism; Gene Expression - drug effects; Gene Expression - immunology; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Humans; In Vitro Techniques; Interleukin-1 - pharmacology; Interleukin-8 - biosynthesis; Interleukin-8 - genetics; Interleukin-8 - metabolism; Lung - cytology; Pancreatic Elastase - pharmacology; Pyrrolidines - pharmacology; RNA, Messenger - analysis; Serine Proteinase Inhibitors - pharmacology; Tosyllysine Chloromethyl Ketone - pharmacology; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00211.2002

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