PMID- 21719740
OWN - NLM
STAT- MEDLINE
DCOM- 20111020
LR  - 20111028
IS  - 1522-1547 (Electronic)
IS  - 0193-1857 (Linking)
VI  - 301
IP  - 3
DP  - 2011 Sep
TI  - Dual effects of interleukin-18: inhibiting hepatitis B virus replication in 
      HepG2.2.15 cells and promoting hepatoma cells metastasis.
PG  - G565-73
LID - 10.1152/ajpgi.00058.2011 [doi]
AB  - Interleukin-18 (IL-18) has been reported to inhibit hepatitis B virus (HBV) 
      replication in the liver of HBV transgenic mice; however, the molecular mechanism 
      of its antiviral effect has not been fully understood. In the present study, it 
      was shown that IL-18 and its receptors (IL-18R) were constitutively expressed in 
      hepatoma cell lines HepG2 and HepG2.2.15 as well as normal liver cell line 
      HL-7702. We demonstrated that IL-18 directly inhibited HBV replication in 
      HepG2.2.15 cells via downregulating the activities of HBV core and X gene 
      promoters. The suppressed HBV replication by IL-18 could be rescued by the 
      administration of BAY11-7082, an inhibitor of transcription factor NF-kappaB. On the 
      other hand, it was of interest that IL-18 promoted HepG2 cell metastasis and 
      migration dose dependently in both wound-healing assays and Transwell assays. The 
      underlying mechanism could be partially attributable to the increased activities 
      of extracellular matrix metalloproteinase (MMP)-9, MMP-3, and MMP-2 by IL-18, 
      which upregulated the mRNA levels of MMP-3 and MMP-9 in a NF-kappaB-dependent manner. 
      Furthermore, it was confirmed that expression of IL-18/IL-18R and most MMPs were 
      remarkably upregulated in hepatocellular carcinoma (HCC) liver cancer tissue 
      specimens, suggesting that IL-18/IL-18R-triggered signaling pathway was closely 
      related to HCC metastasis in vivo. Therefore, we revealed the dual effects of 
      IL-18 in human hepatocytes: it not only inhibited HBV replication but also 
      promoted hepatoma cells metastasis and migration. NF-kappaB played a critical role in 
      both effects. Our work contributed to a deeper understanding of the biological 
      function of IL-18 in human hepatocytes.
FAU - Zhang, Yijuan
AU  - Zhang Y
AD  - State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 
      Wuhan, Hubei, China.
FAU - Li, Yunbo
AU  - Li Y
FAU - Ma, Yifan
AU  - Ma Y
FAU - Liu, Shuhui
AU  - Liu S
FAU - She, Yinglong
AU  - She Y
FAU - Zhao, Peng
AU  - Zhao P
FAU - Jing, Mingzhen
AU  - Jing M
FAU - Han, Tao
AU  - Han T
FAU - Yan, Chao
AU  - Yan C
FAU - Wu, Zhenghui
AU  - Wu Z
FAU - Gao, Jinrong
AU  - Gao J
FAU - Ye, Linbai
AU  - Ye L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110630
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Interleukin-18)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Interleukin-18)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
EIN - Am J Physiol Gastrointest Liver Physiol. 2011 Oct;301(4):G748
MH  - Carcinoma, Hepatocellular/pathology/physiopathology
MH  - Cell Line
MH  - Cell Movement/drug effects
MH  - Hep G2 Cells
MH  - Hepatitis B virus/*drug effects/physiology
MH  - Humans
MH  - Interleukin-18/*physiology
MH  - Liver Neoplasms/pathology/physiopathology
MH  - Matrix Metalloproteinase 3/biosynthesis
MH  - Matrix Metalloproteinase 9/biosynthesis
MH  - NF-kappa B/pharmacology
MH  - Neoplasm Metastasis/physiopathology
MH  - RNA, Messenger/metabolism
MH  - Receptors, Interleukin-18/biosynthesis
MH  - Up-Regulation
MH  - Virus Replication/drug effects
EDAT- 2011/07/02 06:00
MHDA- 2011/10/21 06:00
CRDT- 2011/07/02 06:00
PHST- 2011/07/02 06:00 [entrez]
PHST- 2011/07/02 06:00 [pubmed]
PHST- 2011/10/21 06:00 [medline]
AID - ajpgi.00058.2011 [pii]
AID - 10.1152/ajpgi.00058.2011 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2011 Sep;301(3):G565-73. doi: 
      10.1152/ajpgi.00058.2011. Epub 2011 Jun 30.