Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers discover why eczema often leads to asthma

19.05.2009
Many young children who get a severe skin rash develop asthma months or years later. Doctors call the progression from eczema, or atopic dermatitis, to breathing problems the atopic march.

Now scientists at Washington University School of Medicine in St. Louis have uncovered what might be the key to atopic march. They've shown that a substance secreted by damaged skin circulates through the body and triggers asthmatic symptoms in allergen-exposed laboratory mice.

The findings, published May 19, 2009, in Public Library of Science Biology, suggest that early treatment of skin rash and inhibition of the trigger substance might block asthma development in young patients with eczema.

Fifty percent to 70 percent of children with severe atopic dermatitis go on to develop asthma, studies show. By comparison, the rate of asthma incidence among the general population is only about 9 percent in children and 7 percent in adults. Seventeen percent of U.S. children suffer from atopic dermatitis, although not all cases are considered severe.

"Over the years, the clinical community has struggled to explain atopic march," says study author Raphael Kopan, Ph.D., professor of developmental biology and of dermatology. "So when we found that the skin of mice with an eczema-like condition produced a substance previously implicated in asthma, we decided to investigate further. We found that the mice also suffered from asthma-like responses to inhaled allergens, implicating the substance, called TSLP, as the link between eczema and asthma."

Doctors and scientists had come up with theories to explain why a skin rash is sometimes associated with asthma. Do some people have an immune system disorder that causes an overreaction to allergens that contact the skin and lung airways? Or is it the opposite — do they have defective skin and airways that trigger an excessive immune response?

Kopan's findings suggest the problem starts with damaged or defective skin. The researchers found that cells in damaged skin can secrete TSLP (thymic stromal lymphopoietin), a compound capable of eliciting a powerful immune response. And because the skin is so effective in secreting TSLP into the blood system, the substance travels throughout the body. When it reaches the lungs, it triggers the hypersensitivity characteristic of asthma.

Led by doctoral student Shadmehr (Shawn) Demehri, the researchers studied mice that had been engineered with a genetic defect in patches of their skin. In the affected areas, the typically ordered layers of skin cells were disrupted, creating a condition similar to eczema. These patches were thickened and inflamed. The defective skin secreted TSLP as part of an alarm system alerting the body that its protective barrier function has failed — the substance activates an immune response that fights invaders.

Operating on the assumption that other barrier organs such as the lung will understand this alarm, the researchers tested what happened when the mice with skin defects inhaled an allergen. They found that their lungs reacted strongly — their breathing became labored and their lung tissue took on the traits that mark asthma in humans: mucous secretion, airway muscle contraction, invasion by white blood cells and conversion of lung cells from one type to another. Additional experiments showed that mice that had normal skin but were engineered to overproduce TSLP also developed the asthma-like symptoms.

"We are excited because we've narrowed down the problem of atopic march to one molecule," Kopan says. "We've shown that skin can act as a signaling organ and drive allergic inflammation in the lung by releasing TSLP. Now it will be important to address how to prevent defective skin from producing TSLP. If that can be done, the link between eczema and asthma could be broken."

TSLP is also produced in lungs of asthma patients, and Kopan says that research in the skin could eventually lead to ways to interfere with TSLP made in the lungs and thereby ease asthma development even in cases that aren't linked to eczema.

"This research is a great example of the value of basic research approaches in uncovering the root causes of disease," says Richard Anderson, M.D., Ph.D., of the National Institutes of Health's National Institute of General Medical Sciences, which partially supported the work. "If these mechanisms operate the same way in humans, we could be on our way toward developing new strategies for preventing or treating asthma."

Demehri S, Morimoto M, Holtzman MJ, Kopan R. Skin-derived TSLP triggers progression from epidermal-barrier defects to asthma. Public Library of Science Biology. May 19, 2009.

Funding from the National Institute of General Medical Sciences, Washington University, the Toyobo Biotechnology Foundation Long-term Research Grant and the Japanese Society for the Promotion of Science supported this research.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Gwen Ericson | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Life Sciences:

nachricht Fingerprint' technique spots frog populations at risk from pollution
27.03.2017 | Lancaster University

nachricht Parallel computation provides deeper insight into brain function
27.03.2017 | Okinawa Institute of Science and Technology (OIST) Graduate University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Northern oceans pumped CO2 into the atmosphere

27.03.2017 | Earth Sciences

Fingerprint' technique spots frog populations at risk from pollution

27.03.2017 | Life Sciences

Big data approach to predict protein structure

27.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>