Cytokines differentially regulate ICAM-1 and VCAM-1 expression on human gingival fibroblasts

Clin Exp Immunol. 2006 Jun;144(3):494-502. doi: 10.1111/j.1365-2249.2006.03064.x.


The expression of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) on human gingival fibroblasts (HGF) may be important for migration and retention of inflammatory cells in periodontally diseased tissue. This study aimed to assess which cytokines regulate ICAM-1 and VCAM-1 expression on HGF. Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma enhanced both ICAM-1 and VCAM-1 expression on HGF. Interleukin (IL)-1beta mainly up-regulated ICAM-1 expression. On the other hand, IL-4 and IL-13 enhanced only VCAM-1 expression on HGF. IL-10 did not modulate both ICAM-1 and VCAM-1 expression. Transforming growth factor (TGF)-beta1 enhanced ICAM-1 expression. However, TGF-beta1 inhibited the VCAM-1 expression induced by TNF-alpha or IL-4. Both ICAM-1 and VCAM-1 expression by HGF was inhibited by nuclear factor-kappaB (NF-kappaB) activation inhibitor (MG-132). Mitogen-activated protein kinases (MAPK) inhibitors did not influence ICAM-1 expression induced by TNF-alpha. Interestingly, VCAM-1 expression was enhanced by MEK inhibitor (PD98059) and c-Jun NH2-terminal kinase (JNK) inhibitor (SP600125). These results mean that the balance of cytokines in periodontally diseased tissue may be essential for control of ICAM-1 and VCAM-1 expression on HGF, and the balance of ICAM-1 and VCAM-1 expression might be important for regulation of leucocytes infiltration and retention in periodontally diseased tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cytokines / pharmacology*
  • Cytokines / physiology
  • Drug Synergism
  • Enzyme Inhibitors / pharmacology
  • Fibroblasts / metabolism*
  • Flow Cytometry / methods
  • Gene Expression Regulation / drug effects
  • Gingiva / cytology
  • Gingiva / metabolism*
  • Humans
  • Imidazoles / pharmacology
  • Intercellular Adhesion Molecule-1 / biosynthesis*
  • Intercellular Adhesion Molecule-1 / genetics
  • Leupeptins / pharmacology
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / physiology
  • Pyridines / pharmacology
  • RNA, Messenger / genetics
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Vascular Cell Adhesion Molecule-1 / biosynthesis*
  • Vascular Cell Adhesion Molecule-1 / genetics


  • Cytokines
  • Enzyme Inhibitors
  • Imidazoles
  • Leupeptins
  • NF-kappa B
  • Pyridines
  • RNA, Messenger
  • Recombinant Proteins
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Mitogen-Activated Protein Kinase Kinases
  • SB 203580
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde