Abstract
Aberrant cholangiocyte reactions in response to inflammatory stimuli are important pathogenic factors for the persistent biliary inflammation in patients with cholangiopathies. Overexpression of intercellular cell adhesion molecule-1 (ICAM-1) in cholangiocytes is a common pathological feature in inflammatory cholangiopathies and can promote cholangiocyte interactions with effector lymphocytes in the portal region. In this study, we tested the involvement of miRNA-mediated posttranscriptional regulation in IFN-γ-induced ICAM-1 expression in cholangiocytes. Using both immortalized and nonimmortalized human cholangiocyte cell lines, we found that IFN-γ activated ICAM-1 transcription and increased ICAM-1 protein expression. Inhibition of ICAM-1 transcription could only partially block IFN-γ-induced ICAM-1 expression at the protein level. In silico target prediction analysis revealed complementarity of miR-221 to the 3′-untranslated region of ICAM-1 mRNA. Targeting of ICAM-1 3′-untranslated region by miR-221 resulted in translational repression in cholangiocytes but not ICAM-1 mRNA degradation. Functional inhibition of miR-221 with anti-miR-221 induced ICAM-1 protein expression. Moreover, IFN-γ stimulation decreased miR-221 expression in cholangiocytes in a signal transducer and activator of transcription 1-dependent manner. Transfection of miR-221 precursor abolished IFN-γ-stimulated ICAM-1 protein expression. In addition, miR-221-mediated expression of ICAM-1 on cholangiocytes showed a significant influence on the adherence of cocultured T cells. These findings indicate that both transcriptional and miRNA-mediated post-transcriptional mechanisms are involved in IFN-γ-induced ICAM-1 expression in human cholangiocytes, suggesting an important role for miRNAs in the regulation of cholangiocyte inflammatory responses.
| Original language | English |
|---|---|
| Journal | American Journal of Physiology - Gastrointestinal and Liver Physiology |
| Volume | 298 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2010 |
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All Science Journal Classification (ASJC) codes
- Gastroenterology
- Physiology (medical)
- Physiology
- Hepatology
Cite this
miR-221 suppresses ICAM-1 translation and regulates interferon-γ- induced ICAM-1 expression in human cholangiocytes. / Hu, Guoku; Gong, Ai Yu; Liu, Jun; Zhou, Rui; Deng, Caishu; Chen, Xian-Ming.
In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 298, No. 4, 04.2010.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - miR-221 suppresses ICAM-1 translation and regulates interferon-γ- induced ICAM-1 expression in human cholangiocytes
AU - Hu, Guoku
AU - Gong, Ai Yu
AU - Liu, Jun
AU - Zhou, Rui
AU - Deng, Caishu
AU - Chen, Xian-Ming
PY - 2010/4
Y1 - 2010/4
N2 - Aberrant cholangiocyte reactions in response to inflammatory stimuli are important pathogenic factors for the persistent biliary inflammation in patients with cholangiopathies. Overexpression of intercellular cell adhesion molecule-1 (ICAM-1) in cholangiocytes is a common pathological feature in inflammatory cholangiopathies and can promote cholangiocyte interactions with effector lymphocytes in the portal region. In this study, we tested the involvement of miRNA-mediated posttranscriptional regulation in IFN-γ-induced ICAM-1 expression in cholangiocytes. Using both immortalized and nonimmortalized human cholangiocyte cell lines, we found that IFN-γ activated ICAM-1 transcription and increased ICAM-1 protein expression. Inhibition of ICAM-1 transcription could only partially block IFN-γ-induced ICAM-1 expression at the protein level. In silico target prediction analysis revealed complementarity of miR-221 to the 3′-untranslated region of ICAM-1 mRNA. Targeting of ICAM-1 3′-untranslated region by miR-221 resulted in translational repression in cholangiocytes but not ICAM-1 mRNA degradation. Functional inhibition of miR-221 with anti-miR-221 induced ICAM-1 protein expression. Moreover, IFN-γ stimulation decreased miR-221 expression in cholangiocytes in a signal transducer and activator of transcription 1-dependent manner. Transfection of miR-221 precursor abolished IFN-γ-stimulated ICAM-1 protein expression. In addition, miR-221-mediated expression of ICAM-1 on cholangiocytes showed a significant influence on the adherence of cocultured T cells. These findings indicate that both transcriptional and miRNA-mediated post-transcriptional mechanisms are involved in IFN-γ-induced ICAM-1 expression in human cholangiocytes, suggesting an important role for miRNAs in the regulation of cholangiocyte inflammatory responses.
AB - Aberrant cholangiocyte reactions in response to inflammatory stimuli are important pathogenic factors for the persistent biliary inflammation in patients with cholangiopathies. Overexpression of intercellular cell adhesion molecule-1 (ICAM-1) in cholangiocytes is a common pathological feature in inflammatory cholangiopathies and can promote cholangiocyte interactions with effector lymphocytes in the portal region. In this study, we tested the involvement of miRNA-mediated posttranscriptional regulation in IFN-γ-induced ICAM-1 expression in cholangiocytes. Using both immortalized and nonimmortalized human cholangiocyte cell lines, we found that IFN-γ activated ICAM-1 transcription and increased ICAM-1 protein expression. Inhibition of ICAM-1 transcription could only partially block IFN-γ-induced ICAM-1 expression at the protein level. In silico target prediction analysis revealed complementarity of miR-221 to the 3′-untranslated region of ICAM-1 mRNA. Targeting of ICAM-1 3′-untranslated region by miR-221 resulted in translational repression in cholangiocytes but not ICAM-1 mRNA degradation. Functional inhibition of miR-221 with anti-miR-221 induced ICAM-1 protein expression. Moreover, IFN-γ stimulation decreased miR-221 expression in cholangiocytes in a signal transducer and activator of transcription 1-dependent manner. Transfection of miR-221 precursor abolished IFN-γ-stimulated ICAM-1 protein expression. In addition, miR-221-mediated expression of ICAM-1 on cholangiocytes showed a significant influence on the adherence of cocultured T cells. These findings indicate that both transcriptional and miRNA-mediated post-transcriptional mechanisms are involved in IFN-γ-induced ICAM-1 expression in human cholangiocytes, suggesting an important role for miRNAs in the regulation of cholangiocyte inflammatory responses.
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U2 - 10.1152/ajpgi.00490.2009
DO - 10.1152/ajpgi.00490.2009
M3 - Article
VL - 298
JO - American Journal of Physiology - Gastrointestinal and Liver Physiology
JF - American Journal of Physiology - Gastrointestinal and Liver Physiology
SN - 0193-1857
IS - 4
ER -