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

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

Research output: Contribution to journalArticle

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)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume267
Issue number6 11-6
StatePublished - 1994
Externally publishedYes

Fingerprint

Fibrin
Plasminogen Activator Inhibitor 1
Tumor Necrosis Factor-alpha
Epithelial Cells
Plasminogen Activator Inhibitor 2
Thromboplastin
Tissue Plasminogen Activator
Cytokines
Messenger RNA
Bronchiolitis
Factor Xa
Plasminogen Activators
Plasminogen
Urokinase-Type Plasminogen Activator
Wounds and Injuries
Transforming Growth Factors
Dactinomycin
Fibrinolysis
Infection

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Physiology
  • Pulmonary and Respiratory Medicine

Cite this

Effects of TGF-β and TNF-α on procoagulant and fibrinolytic pathways of human tracheal epithelial cells. / Idell, S.; Kumar, A.; Zwieb, Christian W; Holiday, D.; Koenig, K. B.; Johnson, A. R.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 267, No. 6 11-6, 1994.

Research output: Contribution to journalArticle

Idell, S. ; Kumar, A. ; Zwieb, Christian W ; Holiday, D. ; Koenig, K. B. ; Johnson, A. R. / Effects of TGF-β and TNF-α on procoagulant and fibrinolytic pathways of human tracheal epithelial cells. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 1994 ; Vol. 267, No. 6 11-6.
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