Bile acids regulate RANTES gene expression through its cognate NF-kappaB binding sites.
Regulated upon activation, normal T-cells expressed and secreted (RANTES) mainly migrates memory type CD4+ T-lymphocytes to inflamed tissues. In this study, we examined effects of bile acids on RANTES gene expression in human hepatoma cells. Upon stimulation with hydrophobic bile acids, RANTES proteins were clearly increased. Semiquantitative RT-PCR analysis revealed that chenodeoxycholic acid (CDCA) induced RANTES mRNA expression. Moreover, RANTES was transcriptionally induced in two hepatoma cell lines by CDCA, presumably via its cognate NF-kappaB binding sites in the RANTES promoter. Electrophoretic mobility shift assay revealed that hydrophobic bile acids induced DNA-binding activity of NF-kappaB. Additionally, the magnitude of inducibility was closely associated with the hydrophobicity of bile acids. In conclusion, we might indicate that bile acids induced RANTES gene expression in human hepatoma cells, possibly suggesting that bile acids play an important role in migration of inflammatory cells by RANTES to the liver in patients with primary biliary cirrhosis.
Hirano
F
F
Second Department of Internal Medicine, Asahikawa Medical College, Midorigaoka higashi 2-1, Asahikawa 078-8510, Japan. fhirano@asahikawa-med.ac.jp
Kobayashi
A
A
Hirano
Y
Y
Nomura
Y
Y
Fukawa
E
E
Makino
I
I
D000906:Antibodies / Q000276:immunology; D001647:Bile Acids and Salts / Q000737:chemistry / Q000502:physiology*; D001665:Binding Sites; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008105:Liver Cirrhosis, Biliary / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism* / Q000502:physiology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D000906:Antibodies; D001647:Bile Acids and Salts; D018946:Chemokine CCL5; D016328:NF-kappa B; D012333:RNA, Messenger; D002635:Chenodeoxycholic Acid