Featured Research

from universities, journals, and other organizations

Scientists identify cell death pathway involved in lethal sepsis

Date:
December 22, 2011
Source:
Cell Press
Summary:
Sepsis, a form of systemic inflammation, is the leading cause of death in critically ill patients. Now, a new study finds that inhibition of a specific cell death pathway called "necroptosis" protected mice from lethal inflammation. The research may lead to new therapeutic interventions for fatal inflammatory conditions that are notoriously hard to control.

Sepsis, a form of systemic inflammation, is the leading cause of death in critically ill patients. Sepsis is linked with massive cell death; however, the specific mechanisms involved in the lethality of sepsis are unclear. Now, a new study published by Cell Press in a recent issue of the journal Immunity finds that inhibition of a specific cell death pathway called "necroptosis" protected mice from lethal inflammation. The research may lead to new therapeutic interventions for fatal inflammatory conditions that are notoriously hard to control.

Systemic inflammatory response syndrome (SIRS) is a body-wide inflammatory response that can be caused by an infection, such as in the condition sepsis, or by some sort of physical trauma, such as a severe burn. Sepsis and SIRS are thought to be caused by the cytokine tumor necrosis factor (TNF). However, although research has shown that TNF functions in inflammation, cell death, and survival, the specific mechanisms linking TNF with SIRS are not well understood.

"Engagement of TNF receptor 1 activates two diametrically opposed pathways: survival/inflammation and cell death," explains senior study author, Dr. Peter Vandenabeele, from Ghent University and Flanders Institute for Biotechnology (VIB) in Belgium. "An additional switch decides, depending on the cellular context, between apoptosis and necroptosis, two different cell death pathways. In our study, we explored the involvement of both of these cell death pathways in SIRS."

Dr. Vandenabeele and colleagues found that while disruption of molecules required for apoptosis had no impact on lethal SIRS, inhibition or genetic deletion of RIPK molecules, which are required for necroptosis, provided complete protection against SIRS lethality. Basically, inhibition of one type of cell death did not protect mice from lethal inflammation while disruption of a different cell death pathway improved survival. The researchers went on to confirm their findings in a clinically relevant setting by demonstrating that RIPK deficiency provided protection in a mouse model of peritonitis.

Taken together, the results demonstrate a crucial role for RIPK in sepsis-mediated lethality and uncover potential therapeutic targets for treatment of SIRS and sepsis. "Selectively targeting the necroptosis process may be more advantageous than globally blocking TNF because it leaves space for the important anti-infectious functions of TNF," concludes Dr. Vandenabeele. "New insight into the precise regulatory pathways associated with necroptosis and the molecular interactions involved in the RIPK pathways will provide additional targets for intervention in these high mortality pathological conditions, which have previously been classified as uncontrollable."


Story Source:

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


Journal Reference:

  1. Linde Duprez, Nozomi Takahashi, Filip VanHauwermeiren, Benjamin Vandendriessche, Vera Goossens, Tom VandenBerghe, Wim Declercq, Claude Libert, Anje Cauwels, Peter Vandenabeele. RIP Kinase-Dependent Necrosis Drives Lethal Systemic Inflammatory Response Syndrome. Immunity, 2011; 35 (6): 908 DOI: 10.1016/j.immuni.2011.09.020

Cite This Page:

Cell Press. "Scientists identify cell death pathway involved in lethal sepsis." ScienceDaily. ScienceDaily, 22 December 2011. <www.sciencedaily.com/releases/2011/12/111222133321.htm>.
Cell Press. (2011, December 22). Scientists identify cell death pathway involved in lethal sepsis. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2011/12/111222133321.htm
Cell Press. "Scientists identify cell death pathway involved in lethal sepsis." ScienceDaily. www.sciencedaily.com/releases/2011/12/111222133321.htm (accessed July 22, 2014).

Share This




More Health & Medicine News

Tuesday, July 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Courts Conflicted Over Healthcare Law

Courts Conflicted Over Healthcare Law

AP (July 22, 2014) Two federal appeals courts issued conflicting rulings Tuesday on the legality of the federally-run healthcare exchange that operates in 36 states. (July 22) Video provided by AP
Powered by NewsLook.com
Why Do People Believe We Only Use 10 Percent Of Our Brains?

Why Do People Believe We Only Use 10 Percent Of Our Brains?

Newsy (July 22, 2014) The new sci-fi thriller "Lucy" is making people question whether we really use all our brainpower. But, as scientists have insisted for years, we do. Video provided by Newsy
Powered by NewsLook.com
Scientists Find New Way To Make Human Platelets

Scientists Find New Way To Make Human Platelets

Newsy (July 22, 2014) Boston scientists have discovered a new way to create fully functioning human platelets using a bioreactor and human stem cells. Video provided by Newsy
Powered by NewsLook.com
Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
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:

More Coverage


Targeted Blocking of Cell Death Prevents Fatal Condition Septic Shock, Study Suggests

Dec. 27, 2011 Researchers have discovered a new approach to preventing septic shock, an often fatal extreme inflammatory reaction of the body. It is the most frequent cause of death at intensive care departments ... read more
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