Protein kinase inhibitors modulate time-dependent effects of UV and ionizing irradiation on ICAM-1 expression on human hepatoma cells.
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.
Meineke
V
V
Institute of Radiobiology, Federal Armed Forces Medical Academy, D-80937 Munich, Germany. Viktor.Meineke@t-online.de
Moede
T
T
Gilbertz
K-P
KP
Mayerhofer
A
A
Ring
J
J
Köhn
F-M
FM
Van Beuningen
D
D
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
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