Leukocyte function-associated antigen 1-dependent adhesion of rat hepatoma AH66F cells and inhibition by protein kinase C inhibitors.
When rat ascites hepatoma AH66F cells were incubated on a mesothelial cell (M-cell) layer for 1 hr, the adhesion rate of the cells to M-cells was ca. 46%. The protein kinase C (PKC) inhibitors, N-(2-methylpiperazyl)-5-isoquinolinesulfonamide (H-7) and N-ethoxycarbonyl-7-oxostaurosporine (NA-382), inhibited the adhesion of AH66F cells in a concentration-dependent manner, and the effect of NA-382 appeared after a treatment of more than 24 hr. The decreased adhesion rate after treatment with NA-382 for 48 hr was not further inhibited by addition of monoclonal antibodies of leukocyte function-associated antigen-1 (LFA-1) alpha- and beta-chains and intercellular adhesion molecule-1 (ICAM-1) (WT.1, WT.3, and 1A29, respectively). The expression of LFA- 1 alpha- and beta-chains on the surface of the plasma membrane of AH66F cells was decreased after treatment with NA-382 for 48 hr; treatment with a potent inhibitor of cyclic AMP-dependent protein kinase, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), did not affect the cell adhesion and the expression of LFA-1 molecules on AH66F cells. These results suggest that the expression of LFA-1 molecules on AH66F cells is regulated through the PKC pathway.
Nomura
M
M
Research Laboratory for Development of Medicine, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanagawa-machi, Kanazawa, Japan.
Yamamoto
H
H
Sugiura
N
N
Miyamoto
K
K
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal; D002448:Cell Adhesion / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D019311:Staurosporine / Q000031:analogs & derivatives; D013449:Sulfonamides; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D016169:Lymphocyte Function-Associated Antigen-1; D013449:Sulfonamides; D018799:Intercellular Adhesion Molecule-1; C075317:N-ethoxycarbonyl-7-oxostaurosporine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D019311:Staurosporine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide