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:6/3/2016)... 3, 2016 Das ... Nepal hat ein 44 ... geprägter Kennzeichen, einschließlich Personalisierung, Registrierung und IT-Infrastruktur, ... Produktion und Implementierung von Identitätsmanagementlösungen. Zahlreiche renommierte ... Januar teilgenommen, aber Decatur wurde als konformste ...
(Date:6/2/2016)... Perimeter Surveillance & Detection Systems, ... Infrastructure, Support & Other Service  The latest ... comprehensive analysis of the global Border Security market ... of $17.98 billion in 2016. Now: In ... in software and hardware technologies for advanced video surveillance. ...
(Date:5/20/2016)... 2016  VoiceIt is excited to announce its ... By working together, VoiceIt and VoicePass will ... VoicePass take slightly different approaches to voice biometrics, ... and usability. ... partnership. "This marketing and technology partnership ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... 27, 2016  Global demand for enzymes is ... 2020 to $7.2 billion.  This market includes enzymes ... products, biofuel production, animal feed, and other markets) ... biocatalysts). Food and beverages will remain the largest ... consumption of products containing enzymes in developing regions.  ...
(Date:6/27/2016)... ... June 27, 2016 , ... Newly ... technologies, services and solutions to the healthcare market. The company's primary focus is ... manufacturing, sales and marketing strategies that are necessary to help companies efficiently bring ...
(Date:6/24/2016)... , June 24, 2016 Epic ... sensitively detects cancers susceptible to PARP inhibitors by ... tumor cells (CTCs). The new test has already ... therapeutics in multiple cancer types. Over ... DNA damage response pathways, including PARP, ATM, ATR, ...
(Date:6/23/2016)... , June 23, 2016   Boston ... of novel compounds designed to target cancer stemness ... has been granted Orphan Drug Designation from the ... treatment of gastric cancer, including gastroesophageal junction (GEJ) ... inhibitor designed to inhibit cancer stemness pathways by ...
Breaking Biology Technology: