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Key molecular signaling switch involved in allergic disease identified
October 30, 2006Findings may provide a new target for treatment of allergic reactions
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.
Virginia Commonwealth University
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.
Virginia Commonwealth University
Allergic Disease Current Events and Allergic Disease News RSSNew chromosomal abnormality identified in leukemia associated with Down syndrome
Researchers identified a new chromosomal abnormality in acute lymphoblastic leukemia (ALL) that appears to work in concert with another mutation to give rise to cancer. This latest anomaly is particularly common in children with Down syndrome.
Study Characterizes Eczema Patients Most at Risk for Dangerous Viral Infections
Eczema patients at risk for serious viral infections have more severe disease, are more likely to be allergic to food and other allergens, and have a frequent history of staph infections.
New data analysis shows possible link between childhood obesity and allergies
A new study indicates there may be yet another reason to reduce childhood obesity - it may help prevent allergies. The study published in the May issue of the Journal of Allergy and Clinical Immunology showed that obese children and adolescents are at increased risk of having some kind of allergy, especially to a food.
New risk variant for atopic dermatitis identified
Scientists of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch and Charité - University Medical School, Berlin, Germany, in collaboration with researchers from the Klinikum rechts der Isar of Technical University Munich and Christian Albrecht University, Kiel, have identified a gene variant on chromosome 11 that is associated with an increased risk of atopic dermatitis.
Scientists identify new role for lung epithelial cells in sensing allergens in the air
Researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and at Ghent University in Ghent, Belgium, have identified a new role for certain lung cells in the immune response to airborne allergens.
Fishy diet in early infancy cuts eczema risk
An infant diet that includes fish before the age of 9 months curbs the risk of developing eczema, indicates research published ahead of print in the Archives of Disease in Childhood.
Road pollution blamed for higher allergy risk in kids
New evidence blames traffic-related pollution for increasing the risk of allergy and atopic diseases among children by more than fifty percent. What's more, the closer children live to roads, the higher their risk.
Personalized therapy for asthma and COPD could soon be here
Researchers at Washington University School of Medicine in St. Louis have defined a new type of immune response that is activated in patients with severe asthma and COPD (chronic obstructive pulmonary disease). Their discovery could dramatically improve diagnosis and treatment of patients with chronic inflammatory lung disease.
Eczema still on the increase in developing countries
Experts are warning policy makers that allergic disease might replace infectious disease as a major cause of ill health in cities undergoing rapid demographic changes in developing countries.
Eating apples and fish during pregnancy may protect against childhood asthma and allergies
Women who eat apples and fish during pregnancy may reduce the risk of their children developing asthma or allergic disease, suggests a new study presented at the American Thoracic Society 2007 International Conference, on Sunday, May 20.
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