Featured Research

from universities, journals, and other organizations

The pathway to asthma winds through toll-like receptor 4

Date:
August 15, 2013
Source:
Baylor College of Medicine
Summary:
A molecule called toll-like receptor 4 plays a key role in prompting the innate or immediate response that drives allergic disease and asthma.

The core of a computer is its CPU (central processing unit) or chip. We are looking for the chip that drives allergic disease," said the professor of medicine, chief of the section of immunology, allergy and rheumatology in Baylor College of Medicine's department of medicine and director of the Biology of Inflammation Center at BCM. In a report that appears online in the journal Science, he and colleagues at BCM describe an important component of that chip -- a molecule called toll-like receptor 4 that plays a key role in prompting the innate or immediate response that drives allergic disease and asthma.

Asthma is part of a battle that takes place as the immune system marshals its forces to fight off an invading organism-or what mimics such invaders. The ensuing fight takes a significant toll on the human airway and lungs, often generating a violent and itself potentially deadly reaction -- asthma.

In 2002, Corry and his colleagues found that proteinases, enzymes that chop up other proteins, are important in initiating the adaptive immune response that prompts generation of the critical T-cells and B-cells that populate the adaptive immune system. The adaptive immune system specifically targets allergens, and Corry knew that the more immediate innate immune system also played an important role in asthma and allergy.

"If you take many proteinases and give them to mice, they will induce an allergic disease that resembles asthma," he said.

What links proteinases, asthma?

With that key finding in the adaptive immune system, the researchers turned their attention to the puzzle presented by the innate immune system. "What is the relationship between proteinases and asthma?" he said. Other work in the field pointed to another immune molecule called toll-like receptor 4 that was believed to play a role in activating T-helper type 2 (Th2) cells.

Instead, he and his colleagues found that the proteinases carve up a protein known as fibrinogen, leaving behind fragments that signal through the crucial toll-like receptor 4 to activate the cells of the innate immune system -- the macrophages of the airway and airway epithelia.

"Toll-like receptor 4 is not required for the Th2 response itself," said Corry. "But, the Th2 response is proteinase dependent. When the macrophages are activated by fibrinogen cleavage products in culture, you get beautiful activation," said Corry.

In the airway, the same fibrinogen fragments that are part of the blood clotting process can cause clotting that is a barrier to breathing, said Corry.

Survival mode

In his studies, he used proteinase-producing fungi as the environmental trigger for asthma. Laboratory mice that lacked toll-like receptor 4 did not mount a robust allergic airway disease when challenged by proteinase, viable fungi or other triggers but did have a normal Th2 immunity.

"Why do our bodies do this?" said Corry. The answer is both simple and complicated. The system developed to allow organisms to survive infection with deadly organisms such as fungi. How it achieves that is complicated.

In this "survival mode," the immune system generates symptoms that can themselves create disease.

Against the insidious onslaught of organisms such as fungi, which can kill if left unchecked, asthma may be a better alternative, said Corry.

"If you donΉt fight fungi off, they will get you," he said.


Story Source:

The above story is based on materials provided by Baylor College of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. V. O. Millien, W. Lu, J. Shaw, X. Yuan, G. Mak, L. Roberts, L.-Z. Song, J. M. Knight, C. J. Creighton, A. Luong, F. Kheradmand, D. B. Corry. Cleavage of Fibrinogen by Proteinases Elicits Allergic Responses Through Toll-Like Receptor 4. Science, 2013; 341 (6147): 792 DOI: 10.1126/science.1240342

Cite This Page:

Baylor College of Medicine. "The pathway to asthma winds through toll-like receptor 4." ScienceDaily. ScienceDaily, 15 August 2013. <www.sciencedaily.com/releases/2013/08/130815145144.htm>.
Baylor College of Medicine. (2013, August 15). The pathway to asthma winds through toll-like receptor 4. ScienceDaily. Retrieved April 24, 2014 from www.sciencedaily.com/releases/2013/08/130815145144.htm
Baylor College of Medicine. "The pathway to asthma winds through toll-like receptor 4." ScienceDaily. www.sciencedaily.com/releases/2013/08/130815145144.htm (accessed April 24, 2014).

Share This



More Health & Medicine News

Thursday, April 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Big Pharma Braces for M&A Wave

Big Pharma Braces for M&A Wave

Reuters - Business Video Online (Apr. 22, 2014) — Big pharma on the move as Novartis boss, Joe Jimenez, tells Reuters about plans to transform his company via an asset exchange with GSK, and Astra Zeneca shares surge on speculation that Pfizer is looking for a takeover. Joanna Partridge reports. Video provided by Reuters
Powered by NewsLook.com
Study Says Most Crime Not Linked To Mental Illness

Study Says Most Crime Not Linked To Mental Illness

Newsy (Apr. 22, 2014) — A new study finds most crimes committed by people with mental illness are not caused by symptoms of their illness or disorder. Video provided by Newsy
Powered by NewsLook.com
Hagel Gets Preview of New High-Tech Projects

Hagel Gets Preview of New High-Tech Projects

AP (Apr. 22, 2014) — Defense Secretary Chuck Hagel is given hands-on demonstrations Tuesday of some of the newest research from DARPA _ the military's Defense Advanced Research Projects Agency program. (April 22) Video provided by AP
Powered by NewsLook.com
How Smaller Plates And Cutlery Could Make You Feel Fuller

How Smaller Plates And Cutlery Could Make You Feel Fuller

Newsy (Apr. 22, 2014) — NBC's "Today" conducted an experiment to see if changing the size of plates and utensils affects the amount individuals eat. 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