Keratinocyte growth factor (KGF) decreases ICAM-1 and VCAM-1 cell expression on bronchial epithelial cells

Clin Exp Immunol. 2003 Apr;132(1):61-9. doi: 10.1046/j.1365-2249.2003.02102.x.


Activation of leucocytes during airway inflammatory reaction involves adhesion to bronchial epithelial cells (BEC), a process implicating specific interactions between glycoproteins with epithelial cell surface proteins, mainly intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). In this study, the effect of keratinocyte growth factor (KGF), a growth factor involved in pulmonary epithelium repair, was evaluated on adhesion molecule expression with BEAS-2B cells and BEC and granulocyte adherence to BEAS-2B. The modulation by KGF of membrane and mRNA expression of ICAM-1 and VCAM-1 was studied on confluent cells stimulated or not with tumour necrosis factor-alpha (TNF) (200 UI/ml) or TNF and interleukin (IL)-4 (50 UI/ml and 10 ng/ml). Levels of soluble-(s)ICAM-1 and sVCAM-1 were measured by ELISA. Although moderately, KGF significantly decreased membrane ICAM-1 expression in unstimulated BEAS-2B cells (24% inhibition at 100 ng/ml) or in TNF- or TNF + IL-4-stimulated cells (22.5 and 18.7% inhibition, respectively). Treatment with KGF tended to decrease VCAM-1 expression in TNF- and TNF + IL-4-stimulated BEAS-2B (P = n.s. and P < 0.05, 14 and 15% inhibition, respectively). In primary culture of BEC, adhesion molecule expression was also reduced. ICAM-1 and VCAM-1 mRNA expression were also inhibited by KGF. Levels of sICAM-1 and sVCAM-1 were not significantly increased in supernatants from KGF-treated cells (30% and 24% increase at 100 ng/ml, respectively) compared to controls. Moreover, KGF decreased by 31% the adherence of neutrophils to TNF-activated BEAS-2B. In conclusion, KGF decreases ICAM-1 and VCAM-1 expression and neutrophil adherence in BEC. These suggest its involvement in the resolution of the inflammatory reaction.

MeSH terms

  • Bronchi / immunology*
  • Cell Adhesion / drug effects
  • Cell Line
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology*
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors / pharmacology*
  • Flow Cytometry
  • Humans
  • Intercellular Adhesion Molecule-1 / analysis*
  • Intercellular Adhesion Molecule-1 / genetics
  • Interleukin-4 / pharmacology
  • Neutrophils / cytology
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Statistics, Nonparametric
  • Tumor Necrosis Factor-alpha / pharmacology
  • Vascular Cell Adhesion Molecule-1 / analysis*
  • Vascular Cell Adhesion Molecule-1 / genetics


  • FGF7 protein, human
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Fibroblast Growth Factor 7
  • Intercellular Adhesion Molecule-1
  • Interleukin-4
  • Fibroblast Growth Factors