Navigation Links
Leading cause of death in 'preemies' might be controlled by resetting a molecular switch
Date:12/2/2007

Washington, D.C. -- Blocking signals from a key molecular receptor that normally switches on the intestines immune response but instead becomes too intense in the presence of stress and toxins may help reverse necrotizing enterocolitis (NEC), a leading cause of death in premature newborns, according to scientists at the American Society for Cell Biology 47th annual meeting.

David J. Hackam and his laboratory team at the Childrens Hospital of Pittsburgh report that neonatal mice with inactivating mutations in the Toll-like receptor 4 (TLR4) are protected from NEC. Its a case of defenders becoming unwitting attackers, says Hackam.

Toll-like receptors are key players in the innate immune system. Protruding from enterocytes that form the innermost barrier-like layer of the small and large intestines, TLR4 receptors are primed to recognize pathogenic bacteria and sound the alarm.

But Hackams group found that the stresses of oxygen deprivation and bombardment by bacterial toxins, conditions that can occur in premature infants with underdeveloped lungs, stimulate too much production of TLR4. Like an unstoppable alarm, the increased numbers of TLR4 blare out signals that eventually tip the cells into cellular suicide. They also stop enterocytes from migrating to close wounds in the intestines.

These events, which do not occur in the TLR4-deficient mice, allow NEC to spread as the fragile lining of the gut gives way, releasing a flood of pathogens into the bloodstream. Even with modern advances in neonatal care, NEC affects 20 percent of premature babies and is fatal in nearly half of all cases, according to Hackam.

Hackams group discovered another way to switch off the molecular alarm in mice with NEC by interfering with production of a focal adhesion kinase (FAK) that the researchers found associated with TLR4. By shutting down FAK with small interfering RNA, the TLR4 siren was silenced. Under these conditions, the researchers watched enterocytes regain the ability to migrate, a property important for healing the damaged tissue.

Says Hackam, We hope to develop treatment strategies that allow us to block the TLR4 switch from working⎯perhaps by influencing its interaction with FAK⎯using novel treatments that could be administered as a component of oral feeds.


'/>"/>

Contact: John Fleischman
jfleischman@ascb.org
513-929-4635
American Society for Cell Biology
Source:Eurekalert

Related biology news :

1. M2SYS Partners with SecuGen Corporation to Support Market Leading Hamster Plus Fingerprint Reader with Auto-On Technology
2. Leading experts cite poor health and nutrition as major barrier to education in developing world
3. Ossur -- leading orthopedic pioneer - expands network to Asia
4. Leading researchers to reveal comprehensive dos and donts for prostate cancer
5. BIO-key(R) PocketCop(R) Project Leading the Nation According to Televised Report
6. Are current projections of climate change-impacts on biodiversity misleading?
7. Cleveland Clinic leading clinical program to improve early-stage lung cancer detection
8. deCODE discovers cause of major subtype of glaucoma
9. Study begins to reveal clues to the cause and progression of sepsis
10. Bleeding, not inflammation, is major cause of early lung infection death
11. Gamma globulin effective in treating eye infections caused by adenoviruses
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/16/2016)... YORK , May 16, 2016   EyeLock ... solutions, today announced the opening of an IoT Center ... to strengthen and expand the development of embedded iris ... an unprecedented level of convenience and security with unmatched ... authenticate one,s identity aside from DNA. EyeLock,s platform uses ...
(Date:5/9/2016)... UAE, May 9, 2016 Elevay ... comes to expanding freedom for high net worth professionals ... in today,s globally connected world, there is still no ... could ever duplicate sealing your deal with a firm ... passports by taking advantage of citizenship via investment programs ...
(Date:4/28/2016)... and BANGALORE, India , April 28, 2016 ... a product subsidiary of Infosys (NYSE: INFY ), ... a global partnership that will provide end customers ... mobile banking and payment services.      (Logo: ... innovation area for financial services, but it also plays a ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... 2016 /PRNewswire/ - FACIT has announced the creation ... biotechnology company, Propellon Therapeutics Inc. ("Propellon" or "the ... a portfolio of first-in-class WDR5 inhibitors for the ... WDR5 represent an exciting class of therapies, possessing ... for cancer patients. Substantial advances have been achieved ...
(Date:6/23/2016)...  The Biodesign Challenge (BDC), a university competition that ... living systems and biotechnology, announced its winning teams at ... New York City . The teams, ... at MoMA,s Celeste Bartos Theater during the daylong summit. ... curator of architecture and design, and Suzanne Lee ...
(Date:6/23/2016)... June 23, 2016 Apellis Pharmaceuticals, Inc. ... clinical trials of its complement C3 inhibitor, APL-2. ... multiple ascending dose studies designed to assess the ... subcutaneous injection in healthy adult volunteers. ... as a single dose (ranging from 45 to ...
(Date:6/23/2016)... ... June 23, 2016 , ... ... and technical consulting, provides a free webinar on Performing Quality Investigations: ... 2016 at 12pm CT at no charge. , Incomplete investigations are still a ...
Breaking Biology Technology: