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 September 21, 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 September 21, 2014).

Share This



More Health & Medicine News

Sunday, September 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Sierra Leone's Nationwide Ebola Curfew Underway

Sierra Leone's Nationwide Ebola Curfew Underway

Newsy (Sep. 20, 2014) Sierra Leone is locked down as aid workers and volunteers look for new cases of Ebola. Video provided by Newsy
Powered by NewsLook.com
Changes Found In Brain After One Dose Of Antidepressants

Changes Found In Brain After One Dose Of Antidepressants

Newsy (Sep. 19, 2014) A study suggest antidepressants can kick in much sooner than previously thought. Video provided by Newsy
Powered by NewsLook.com
Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
Powered by NewsLook.com
Jury Delivers Verdict in Salmonella Trial

Jury Delivers Verdict in Salmonella Trial

AP (Sep. 19, 2014) A federal jury has convicted three people in connection with an outbreak of salmonella poisoning five years ago that sickened hundreds of people and was linked to a number of deaths. (Sept. 19) Video provided by AP
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