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

Hiroki Numanami, Sekiya Koyama, Esturo Sato, Masayuki Haniuda, Dan K. Nelson, Jeffrey C. Hoyt, Jon L. Freels, Michael P. Habib, Richard A. Robbins

    Research output: Contribution to journalArticlepeer-review

    16 Scopus citations


    Chemotactic chemokines can be released from lung fibroblasts in response to interleukin (IL)-1β and tumor necrosis factor (TNF)-α. 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, α1-antitrypsin, or Nα-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 colonystimulating factor, from HFL-1, were evaluated in response to IL-1β and TNF-α. 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-1β and TNF-α may stimulate lung fibroblasts to release NCA and MCA by a proteasedependent mechanism and that serine protease inhibitors may attenuate the release.

    Original languageEnglish (US)
    Pages (from-to)L882-L890
    JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
    Issue number5 28-5
    StatePublished - May 1 2003


    • Granulocyte/macrophage colony-timulating factor
    • Interleukin-8
    • Monocyte
    • Monocyte chemoattractant protein-1
    • Neutrophil

    ASJC Scopus subject areas

    • Physiology
    • Pulmonary and Respiratory Medicine
    • Physiology (medical)
    • Cell Biology


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