Synergistic effect of SCF and TNF-alpha on the up-regulation of cell-surface expression of ICAM-1 on human leukemic mast cell line (HMC)-1 cells

J Leukoc Biol. 2005 Jul;78(1):239-47. doi: 10.1189/jlb.0704400. Epub 2005 Mar 30.

Abstract

Intercellular adhesion molecule-1 (ICAM-1) has been shown to play crucial roles in mast cell interaction with other inflammatory cells and recruitment into the inflamed tissue. In the present study, human mast cell line-1 (HMC-1) was stimulated with different cytokines including stem cell factor (SCF), tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-13, IL-18, and IL-25. Cell-surface expression of ICAM-1 was assessed by flow cytometry. To elucidate the intracellular signal transduction regulating the ICAM-1 expression, phosphorylated extracellular signal-regulated kinase (ERK), phosphorylated p38 mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-kappaB translocation were assessed by enzyme-linked immunosorbent assay. Results showed that SCF, TNF-alpha, and IL-13 but not IL-18 and IL-25 could up-regulate the surface expression of ICAM-1 on HMC-1 cells. A synergistic effect of SCF and TNF-alpha on ICAM-1 expression was demonstrated. This synergistic effect was shown to be dose-dependently enhanced by SCF but not TNF-alpha. Results indicated that SCF activated ERK, and TNF-alpha activated the p38 MAPK and NF-kappaB pathway. Selective inhibitor of ERK, PD098059, and c-kit inhibitors, STI571 and PP1, suppressed the combined SCF and TNF-alpha-induced ICAM-1 expression. BAY117082 but not SB203580, which are the inhibitors of NF-kappaB and p38 MAPK, respectively, suppressed the TNF-alpha-induced ICAM-1 expression. Therefore, SCF and TNF-alpha acted through ERK and the NF-kappaB pathway to regulate the ICAM-1 expression and elicited the synergistic effect. In conclusion, our results provide insight for cross-talk between different signaling pathways that can help in understanding the fine control of adhesion molecule expression under the concerted effects of cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion / drug effects
  • Cell Adhesion / immunology
  • Cell Communication / drug effects
  • Cell Communication / immunology
  • Cell Line, Tumor
  • Cell Membrane / drug effects
  • Cell Membrane / immunology*
  • Cell Membrane / metabolism
  • Chemotaxis, Leukocyte / drug effects
  • Chemotaxis, Leukocyte / immunology
  • Drug Synergism
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Inflammation / immunology
  • Inflammation / physiopathology
  • Intercellular Adhesion Molecule-1 / drug effects
  • Intercellular Adhesion Molecule-1 / immunology*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-13 / immunology
  • Interleukin-13 / pharmacology
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / immunology
  • Mast Cells / drug effects
  • Mast Cells / immunology*
  • Mast Cells / metabolism
  • Mitogen-Activated Protein Kinase 3 / drug effects
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / immunology
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Stem Cell Factor / immunology*
  • Stem Cell Factor / pharmacology
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / immunology*
  • Up-Regulation / drug effects
  • Up-Regulation / immunology
  • p38 Mitogen-Activated Protein Kinases / drug effects
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Enzyme Inhibitors
  • Interleukin-13
  • NF-kappa B
  • Receptors, Cell Surface
  • Stem Cell Factor
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases