| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
* Institute of Microbiology and Immunology, National Yang-Ming University;
Department of Medical Research and Education, Taipei Veterans General Hospital; and
Division of Intramural Research Affairs, National Health Research Institute, Taipei, Taiwan, Republic of China; and
Department of Applied Medical Sciences, University of Southern Maine, Portland, ME 04104
IL-4 has been known as a Th2 cytokine and can act on B cells, T cells, and monocytes. In this study we demonstrate that IL-4Rs are expressed on human hepatocellular carcinoma (HCC) cells. We found that IL-4 suppresses hepatitis B surface Ag (HBsAg) mRNA and HBsAg production in the Hep3B cell line, which contains an integrated hepatitis B virus (HBV) genome and constitutively secretes HBsAg. When Hep3B cells are further transfected with the plasmid pHBV3.6 that contains >1 U of HBV genome, IL-4 could suppress the production of all HBV RNA and secreted HBsAg and hepatitis B virus e Ag. Furthermore, an endogenous DNA polymerase activity assay shows a decrease in HBV DNA after IL-4 treatment. Using luciferase reporter assays we have demonstrated that IL-4 could suppress the activity of the surface promoter II and the core promotor (CP). To delineate how IL-4 suppressed the transcription of HBV genes, we have examined the effect of IL-4 on the expression of transcription factors that are known to bind to the core upstream regulatory sequence, which colocalizes with enhancer II of the HBV genome. Our results demonstrate that IL-4 suppresses the expression of C/EBP
. Furthermore, overexpression of C/EBP blocked 43 and 30% of the IL-4-mediated suppression of CP activity and IL-4-induced suppression of pregenomic RNA, respectively. Finally, we have demonstrated that mutations affecting the C/EBP-binding sites on core upstream regulatory sequence/enhancer II completely abolish the IL-4-mediated suppression of CP activity. Thus, down-regulation of C/EBP may be involved in the anti-HBV effect of IL-4 in Hep3B cells.
This article has been cited by other articles:
|
|
 |
|
  A. Budhu and X. W. Wang The role of cytokines in hepatocellular carcinoma J. Leukoc. Biol., December 1, 2006; 80(6): 1197 - 1213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Borger, M. Tamm, J. L. Black, and M. Roth Asthma: Is It Due to an Abnormal Airway Smooth Muscle Cell? Am. J. Respir. Crit. Care Med., August 15, 2006; 174(4): 367 - 372. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
