Featured Research

from universities, journals, and other organizations

Elevated Lymphotoxin Expression In Liver Leads To Chronic Hepatitis And Causes HCC

Date:
October 5, 2009
Source:
Cell Press
Summary:
A recent study maps the pathway that leads from infection with hepatitis B and C virus to chronic hepatitis and liver cancer and proposes a new therapeutic strategy for treating liver diseases with chronic inflammation. The research describes a signaling pathway that can be beneficial during liver regeneration, but can lead to chronic hepatitis and severe liver damage when chronically activated.

A recent study maps the pathway that leads from infection with Hepatitis B and C virus (HBV and HCV) to chronic hepatitis and liver cancer and proposes a new therapeutic strategy for treating liver diseases with chronic inflammation. The research, published by Cell Press in the October issue of the journal Cancer Cell, describes a signaling pathway that can be beneficial during liver regeneration, but can lead to chronic hepatitis and severe liver damage when chronically activated.

The research was performed in the Department of Pathology, Institutes of Clinical Pathology and Neuropathology at the University Hospital in Zurich.

HBV and HCV cause chronic hepatitis and can lead to hepatocellular carcinoma (HCC), the most prevalent primary liver cancer in humans. "Although aberrant expression of cytotoxic cytokines is thought to be critically involved in hepatitis-induced liver cancer, the exact mechanisms driving this progression remain elusive," explains senior study author Dr. Mathias Heikenwalder.

The cytokines lymphotoxin (LT) α and β are mainly produced by white blood cells called lymphocytes and play an important role in organ development and control of the immune response. Previous work had shown that, when compared with normal livers, HCV-infected livers exhibit dramatically increased expression of LTαβ. Dr. Heikenwalder's laboratory, in collaboration with the laboratory of Professor Adriano Aguzzi and colleagues investigated a possible causal relationship between aberrant sustained hepatic LT signaling, chronic hepatitis and the development of HCC.

The researchers found that LTα, LTβ and the LT receptor (LTβR) were upregulated in HBV- or HCV-induced hepatitis and HCC and identified both lymphocytes and liver cells called hepatocytes as the main expressing cells. Liver specific expression of LTα and LTβ induced chronic liver inflammation and HCC in mice. It was the hepatocytes themselves which were the major LT-responsive liver cells and, importantly, when LTβR signaling was blocked in mice with chronic hepatitis, inflammation was partially attenuated and HCC was prevented.

It appears as if LTβR signaling might be beneficial in some cases and detrimental in others. Previous work has shown that LTβR signaling in liver cells supported liver regeneration. However, as is evidenced in this study, there is a causal link between chronic LTβR signaling and both chronic hepatitis and HCC development.

Taken together, the findings indicate that sustained LTβR signaling in liver leads to chronic hepatitis-induced HCC. "Our results show that LT signaling is critically involved in the development of chronic hepatitis and subsequent HCC formation and imply that blocking LTβR signaling might become a beneficial therapeutic approach in the context of HBV- or HCV-induced chronic hepatitis and other liver diseases displaying sustained hepatic LTβR signaling," concludes Dr. Heikenwalder.

The researchers include Johannes Haybaeck, University Hospital Zurich, Zurich, Switzerland; Nicolas Zeller, University Hospital Zurich, Zurich, Switzerland; Monika Julia Wolf, University Hospital Zurich, Zurich, Switzerland; Achim Weber, University Hospital Zurich, Zurich, Switzerland; Ulrich Wagner, University Zurich, Zurich, Switzerland; Michael Odo Kurrer, Cantonal Hospital Aarau, Aarau, Switzerland; Juliane Bremer, University Hospital Zurich, Zurich, Switzerland; Giandomenica Iezzi, Swiss Federal Institute of Technology (ETH), Zurich, Schlieren, Switzerland; Rolf Graf, University Hospital Zurich, Zurich, Switzerland; Pierre-Alain Clavien, University Hospital Zurich, Zurich, Switzerland; Robert Thimme, University of Freiburg, Freiburg, Germany; Hubert Blum, University of Freiburg, Freiburg, Germany; Sergei A. Nedospasov, Engelhardt Institute of Molecular Biology, Moscow, Russia, German Rheumatism Research Center, Berlin, Germany; Kurt Zatloukal, Institute of Pathology, Medical University of Graz, Graz, Austria; Muhammad Ramzan, INSERM and Universite´ Joseph Fourier-Grenoble, Grenoble, France; Sandra Ciesek, Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany; Thomas Pietschmann, Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany; Patrice N. Marche, INSERM and Universite´ Joseph Fourier-Grenoble, Grenoble, France; Michael Karin, University of California, San Diego and University of California, Los Angeles, CA; Manfred Kopf, Swiss Federal Institute of Technology (ETH), Zurich, Schlieren, Switzerland; Jeffrey L. Browning, Biogen Idec, Cambridge, MA; Adriano Aguzzi, University Hospital Zurich, Zurich, Switzerland; and Mathias Heikenwalder, University Hospital Zurich, Zurich, Switzerland.


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Cite This Page:

Cell Press. "Elevated Lymphotoxin Expression In Liver Leads To Chronic Hepatitis And Causes HCC." ScienceDaily. ScienceDaily, 5 October 2009. <www.sciencedaily.com/releases/2009/10/091005123036.htm>.
Cell Press. (2009, October 5). Elevated Lymphotoxin Expression In Liver Leads To Chronic Hepatitis And Causes HCC. ScienceDaily. Retrieved August 30, 2014 from www.sciencedaily.com/releases/2009/10/091005123036.htm
Cell Press. "Elevated Lymphotoxin Expression In Liver Leads To Chronic Hepatitis And Causes HCC." ScienceDaily. www.sciencedaily.com/releases/2009/10/091005123036.htm (accessed August 30, 2014).

Share This




More Health & Medicine News

Saturday, August 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

3 Things To Know About The Ebola Outbreak's Progression

3 Things To Know About The Ebola Outbreak's Progression

Newsy (Aug. 29, 2014) — Here are three things you need to know about the deadly Ebola outbreak's progression this week. Video provided by Newsy
Powered by NewsLook.com
Killer Amoeba Found in Louisiana Water System

Killer Amoeba Found in Louisiana Water System

AP (Aug. 28, 2014) — State health officials say testing has confirmed the presence of a killer amoeba in a water system serving three St. John the Baptist Parish towns. (Aug. 28) Video provided by AP
Powered by NewsLook.com
Who Could Be Burnt by WHO's E-Cigs Move?

Who Could Be Burnt by WHO's E-Cigs Move?

Reuters - Business Video Online (Aug. 28, 2014) — The World Health Organisation has called for the regulation of electronic cigarettes as both tobacco and medical products. Ciara Lee looks at the impact of the move on the tobacco industry. Video provided by Reuters
Powered by NewsLook.com
CDC Director On Ebola Outbreak: 'It's Worse Than I Feared'

CDC Director On Ebola Outbreak: 'It's Worse Than I Feared'

Newsy (Aug. 28, 2014) — CDC director Tom Frieden says the Ebola outbreak is even worse than he feared. But he also said there's still hope to contain it. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins