title: Protein kinase inhibitors modulate time-dependent effects of UV and ionizing irradiation on ICAM-1 expression on human hepatoma cells.
abstract: OBJECTIVE
  To investigate modulation of the expression of the adhesion protein ICAM-1 by UV and ionizing irradiation.
  
  
  METHODS
  HepG2 hepatoma cells were irradiated in vitro with UVB (20 mJ cm(-2)) or X-rays (5 Gy), respectively. Gene expression of ICAM-1 after irradiation was quantified by RT-PCR. Cell surface density of ICAM-1 was determined by flow cytometry. Protein or lipid kinase inhibitors were used to clarify radiation-induced transduction pathways that control ICAM-1 expression. Immuno-electron microscopy and dot-blot analysis were used to examine localization of ICAM-1.
  
  
  RESULTS
  The study showed time-dependent effects of ionizing and UV irradiation on ICAM-1 expression of HepG2 cells. After an immediate transient decrease of ICAM-1 cell surface expression within minutes to hours, ICAM-1 expression increased up to 1.35-fold over normal level at 48 h post-irradiation. Irradiation caused ICAM-1 to become internalized into lysosomes. Additionally, ICAM-1 together with parts of the cell were pinched off. Finally, ICAM-1 levels were down- and up-regulated by decreased or increased gene expression. The early decrease of ICAM-1 expression could be blocked by a potent PKC inhibitor (BisX), whereas the increase of ICAM-1 after 24 h was prevented by addition of the p38 MAP kinase inhibitor SB 203580.
  
  
  CONCLUSIONS
  The data suggest that ICAM-1 expression is modulated by UV, as well as ionizing radiation, in a time-dependent way involving PKC and p38 MAP kinase pathways.
authors.affiliation: Institute of Radiobiology, Federal Armed Forces Medical Academy, D-80937 Munich, Germany. Viktor.Meineke@t-online.de
authors.forename: V
authors.initials: V
authors.lastname: Meineke
authors.forename: T
authors.initials: T
authors.lastname: Moede
authors.forename: K-P
authors.initials: KP
authors.lastname: Gilbertz
authors.forename: A
authors.initials: A
authors.lastname: Mayerhofer
authors.forename: J
authors.initials: J
authors.lastname: Ring
authors.forename: F-M
authors.initials: FM
authors.lastname: Köhn
authors.forename: D
authors.initials: D
authors.lastname: Van Beuningen
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000532:radiotherapy*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis* / Q000235:genetics; D008113:Liver Neoplasms / Q000737:chemistry / Q000532:radiotherapy*; D016253:Microscopy, Immunoelectron; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D004791:Enzyme Inhibitors; D018799:Intercellular Adhesion Molecule-1; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases