UCSF Team Identifies Two Key Molecules In Asthma; Important Finding For New Therapies That Treat Disease At Cell Level

December 17, 1998

Researchers at the University of California San Francisco have identified two molecules that cause cells to cause asthma--a finding that paves the way for developing more effective drugs for treatment.

The molecules connect with a specific cell receptor to alter cellular structure and set up the mechanism of disease.

"It's like finding the words that connect with the ear that enable the process of hearing to be set in motion. Now we can direct further research into how to manipulate these molecules at the outset to change the outcome of the disease," said David B. Corry, MD, an assistant professor of medicine with the UCSF Lung Biology Center at San Francisco General Hospital Medical Center.

Corry is senior investigator of the study, which is reported in the current issue (December 18) of Science. Scientists nationwide have long focused on trying to understand asthma at the cellular level, and the finding is viewed as a significant breakthrough.

The UCSF researchers conducted the study in a mouse model that mimics human asthma.

The team found that disease begins with the presence in lung tissue of two molecules, interleukin-4 and interleukin-13, which then link up with a certain receptor, named the IL-4 receptor alpha. The molecules are hormone-like substances, called cytokines, produced by CD4+ T cells. The receptor is on the surface of these cells and of cells that make up the lung tissue. CD4 cells are the cells that coordinate the overall action of the human immune system, and cytokines modulate this activity.

It is not known why some people have the two molecules--which are known by the shorthand names of IL-4 and IL-13--in their lungs, but it believed to be linked to a genetic predisposition, Corry said.

"The striking message in the scientific investigation is that all the complexity of asthma as a disease comes down to these three elements: molecule, molecule, receptor," Corry added. The research is part of ongoing work over the past 20 years by the UCSF Lung Biology Center.

Asthma affects nearly 12.5 million Americans, including 4.8 million children, and the incidence has been rising dramatically in recent years.

People with asthma have airway passages that are chronically inflamed. The inflammation leaves the airways particularly sensitive to allergens, viruses, or environmental factors like dust or tobacco smoke. Exercise, in particular, can trigger an asthma attack, in which the passages constrict and breathing is difficult.

"Current therapies treat only the symptoms of asthma, so with our new understanding we are excited about the possibilities of moving toward treatments that control the disease from its point of origin," said Gabriele Grünig, DVM,PhD, UCSF postdoctoral visiting scientist and principal author of the Science paper.

It is hoped that new treatments also will be able to avoid some of the side effects associated with current therapies, such as water retention in the tissues or a generally depressed immune system.

One scientific theory has proposed that cellular response to the inflammation creates the narrowing of the air passageway, but the UCSF findings show it is the other way around, Grünig said.

The UCSF team found that the molecule/receptor connection initiates the inflammation and also increases the number of a particular type of cell known as a goblet cell, which produces excessive amounts of mucus in the airway passages during an asthma attack.

One interesting aspect of IL-4 and IL-13 is that they appear to be detrimental only in lung tissue. In other parts of the body, they perform good works, according to Corry. In the gut, for example, they play a key role in eliminating parasites and preventing related disease.

UCSF co-investigators on the study team were Rajeev Venkayya, MD; Dean Sheppard, MD; Martha Warnock, MD; Adil E. Wakil, MD; Markus Mohrs, PhD; and Richard M. Locksley, MD. Additional researchers were Frank Brombacher, PhD, Groote Schuur Hospital/University of Cape Town, South Africa; Donna M. Rennick, PhD, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto; and Debra D. Donaldson, PhD, Genetics Institute, Cambridge, Mass.

The study was funded by grants from the National Institutes of Health, Crohn's and Colitis Foundation, and Hefni Scholars Funds.
Note to journalists: For copies of the complete Science article, contact the News and Information Office of the American Association for the Advancement of Science at 202-326-6440.

University of California - San Francisco

Related Asthma Articles from Brightsurf:

Breastfeeding and risks of allergies and asthma
In an Acta Paediatrica study, exclusive breastfeeding for the first 3 months was linked with a lower risk of respiratory allergies and asthma when children reached 6 years of age.

Researchers make asthma breakthrough
Researchers from Trinity College Dublin have made a breakthrough that may eventually lead to improved therapeutic options for people living with asthma.

Physics vs. asthma
A research team from the MIPT Center for Molecular Mechanisms of Aging and Age-Related Diseases has collaborated with colleagues from the U.S., Canada, France, and Germany to determine the spatial structure of the CysLT1 receptor.

New knowledge on the development of asthma
Researchers at Karolinska Institutet in Sweden have studied which genes are expressed in overactive immune cells in mice with asthma-like inflammation of the airways.

Eating fish may help prevent asthma
A scientist from James Cook University in Australia says an innovative study has revealed new evidence that eating fish can help prevent asthma.

Academic performance of urban children with asthma worse than peers without asthma
A new study published in Annals of Allergy, Asthma and Immunology shows urban children with poorly controlled asthma, particularly those who are ethnic minorities, also suffer academically.

Asthma Controller Step Down Yardstick -- treatment guidance for when asthma improves
The focus for asthma treatment is often stepping up treatment, but clinicians need to know how to step down therapy when symptoms improve.

Asthma management tools improve asthma control and reduce hospital visits
A set of comprehensive asthma management tools helps decrease asthma-related visits to the emergency department, urgent care or hospital and improves patients' asthma control.

Asthma linked to infertility but not among women taking regular asthma preventers
Women with asthma who only use short-acting asthma relievers take longer to become pregnant than other women, according to research published in the European Respiratory Journal.

What are the best ways to diagnose and manage asthma?
A team of experts from The University of Texas Medical Branch at Galveston examined the current information available from many different sources on diagnosing and managing mild to moderate asthma in adults and summarized them.

Read More: Asthma News and Asthma Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.