Key Signaling Switch Identified in Allergic Disease

Oct 30, 2006

A research team has identified a key enzyme responsible for triggering a chain of events that results in allergic reaction, according to new study findings published online this week in Nature Immunology.

The work by researchers from Virginia Commonwealth University, the Hospital for Special Surgery and Weill Cornell Medical College in New York sets the stage for development of new strategies and target therapies that control allergic disease – the sixth leading cause of chronic disease in the United States.

Allergic diseases such as asthma and hay fever are problematic for about 30 percent of the population in the developed world. Researchers have developed various treatments to control allergy, but no cure has been found.

The team has demonstrated, for the first time, the role of a proteolytic enzyme called ADAM10 that releases a major allergy regulatory protein from the surface of cells and thereby promotes a stronger allergic response. The identification of drugs that inhibit ADAM10’s ability to release this molecule could revolutionize treatment of asthma and allergic disease.

“Our research, for the first time, may represent a treatment strategy to prevent, rather than simply control IgE-mediated allergy,” said Daniel Conrad, Ph.D., a professor in VCU’s Department of Microbiology and Immunology. Conrad directed the research conducted at VCU. IgE is an antibody known to trigger Type I allergic disease.

“Understanding ADAM10’s role in allergic disease makes it a potential target for the design of drugs to treat asthma and allergic disease,” he said.

According to Conrad, the outcome of allergic disease can be modulated by high levels of the regulatory protein, known as CD23, which ultimately results in a decreased production of IgE. He said that when the regulatory protein is released from the cell surface by ADAM10 there is an increase in the production of IgE and therefore, increased allergy.

“These exciting results extend the known functions of ADAMs in development and disease. We hope our results will stimulate new research into how to block or activate the function of ADAMs involved in human disease, including allergic response, cancer and rheumatoid arthritis,” said Carl P. Blobel, M.D., Ph.D, chair of the Arthritis and Tissue Degeneration Program at the Hospital for Special Surgery, and professor of Medicine and of Physiology and Biophysics at Weill Cornell Medical College. Blobel directed the research conducted at Weill Cornell.

According to Blobel, in addition to the critical role of ADAM10 in allergic disease through processing of CD23, ADAMs are also key molecules in cancer and rheumatoid arthritis. For example, he said, ADAMs are essential for activating the epidermal growth factor receptor, an established target for the treatment of cancers, such as colon cancer. Moreover, ADAMs release tumor necrosis factor alpha, currently the major target for treatment of rheumatoid arthritis.

Since the 1970s Conrad has been investigating the basic mechanism involved in allergic disease. Blobel has been investigating ADAM proteases since their discovery in the early 1990s.

Source: Virginia Commonwealth University

Explore further: Infant cooing, babbling linked to hearing ability

add to favorites email to friend print save as pdf

Related Stories

Recommended for you

Infant cooing, babbling linked to hearing ability

7 hours ago

Infants' vocalizations throughout the first year follow a set of predictable steps from crying and cooing to forming syllables and first words. However, previous research had not addressed how the amount ...

Developing 'tissue chip' to screen neurological toxins

8 hours ago

A multidisciplinary team at the University of Wisconsin-Madison and the Morgridge Institute for Research is creating a faster, more affordable way to screen for neural toxins, helping flag chemicals that ...

Gene mutation discovered in blood disorder

12 hours ago

An international team of scientists has identified a gene mutation that causes aplastic anemia, a serious blood disorder in which the bone marrow fails to produce normal amounts of blood cells. Studying a family in which ...

Airway muscle-on-a-chip mimics asthma

14 hours ago

The majority of drugs used to treat asthma today are the same ones that were used 50 years ago. New drugs are urgently needed to treat this chronic respiratory disease, which causes nearly 25 million people ...

User comments : 0