Effects of TGF-β and TNF-α on procoagulant and fibrinolytic pathways of human tracheal epithelial cells

S. Idell, A. Kumar, C. Zwieb, D. Holiday, K. B. Koenig, A. R. Johnson

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

The epithelial lining of the airways is subject to injury through several processes, including infections, bronchiolitis, and fume exposures. Because airway fibrin deposition influences the course of local injury, we examined how two inflammatory cytokines influenced fibrin formation and clearance in human tracheal epithelial cells (TEC). TEC were treated with transforming growth factor-β and tumor necrosis factor-α (TNF-α). TNF-α increased release of tissue factor (TF)-related procoagulant activity that, through generation of factor Xa, promotes assembly of the prothrombinase complex at the cell surface. Fibrinolytic activity was plasminogen dependent and due to both urokinase (uPA) and tissue plasminogen activator (tPA). The cells expressed plasminogen activator inhibitor 1 (PAI-1), but relatively little PAI-2. Depression of fibrinolysis by TGF-β correlated with increased PAI-1. Conversely, TNF-α increased plasminogen activator (PA) activity due to increased uPA. Fibrinolytic activity was inhibited by actinomycin D and cyclohexamide, but changes in mRNAs for uPA, tPA, PAI-1, and TF by either cytokine were not appreciable. PAI-2 mRNA was not found. The data indicate that TGF-β decreases the fibrinolytic capacity of TEC, suggesting that this cytokine promotes fibrin retention. TNF-α increases expression of both procoagulant and fibrinolytic activities; this differential regulation could favor both pericellular fibrin formation and dissolution.

Original languageEnglish (US)
Pages (from-to)L693-L703
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume267
Issue number6 11-6
DOIs
StatePublished - 1994
Externally publishedYes

Keywords

  • airway epithelium
  • coagulation
  • fibrinolysis
  • tissue factor
  • tissue plasminogen activator
  • urokinase

ASJC Scopus subject areas

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

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