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

Date:
December 18, 1998
Source:
University Of California San Francisco
Summary:
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.

Researchers at the University of California San Franciscohave identified two molecules that cause cells to causeasthma--a finding that paves the way for developing moreeffective drugs for treatment.

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

"It's like finding the words that connect with the ear thatenable the process of hearing to be set in motion. Now wecan direct further research into how to manipulate thesemolecules at the outset to change the outcome of thedisease," said David B. Corry, MD, an assistant professor ofmedicine with the UCSF Lung Biology Center at San FranciscoGeneral Hospital Medical Center.

Corry is senior investigator of the study, which is reportedin the current issue (December 18) of Science. Scientistsnationwide have long focused on trying to understand asthmaat the cellular level, and the finding is viewed as asignificant breakthrough.

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

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

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

"The striking message in the scientific investigation isthat all the complexity of asthma as a disease comes down tothese three elements: molecule, molecule, receptor," Corryadded. The research is part of ongoing work over the past20 years by the UCSF Lung Biology Center.

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

People with asthma have airway passages that are chronicallyinflamed. The inflammation leaves the airways particularlysensitive to allergens, viruses, or environmental factorslike dust or tobacco smoke. Exercise, in particular, cantrigger an asthma attack, in which the passages constrictand breathing is difficult.

"Current therapies treat only the symptoms of asthma, sowith our new understanding we are excited about thepossibilities of moving toward treatments that control thedisease from its point of origin," said Gabriele Grünig,DVM,PhD, UCSF postdoctoral visiting scientist and principalauthor of the Science paper.

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

One scientific theory has proposed that cellular response tothe inflammation creates the narrowing of the airpassageway, but the UCSF findings show it is the other wayaround, Grünig said.

The UCSF team found that the molecule/receptor connectioninitiates the inflammation and also increases the number ofa particular type of cell known as a goblet cell, whichproduces excessive amounts of mucus in the airway passagesduring an asthma attack.

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

UCSF co-investigators on the study team were RajeevVenkayya, 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, GrooteSchuur Hospital/University of Cape Town, South Africa; DonnaM. Rennick, PhD, DNAX Research Institute of Molecular andCellular Biology, Palo Alto; and Debra D. Donaldson, PhD,Genetics Institute, Cambridge, Mass.

The study was funded by grants from the National Institutesof Health, Crohn's and Colitis Foundation, and HefniScholars Funds.

Note to journalists: For copies of the complete Sciencearticle, contact the News and Information Office of theAmerican Association for the Advancement of Science at202/326-6440.


Story Source:

The above story is based on materials provided by University Of California San Francisco. Note: Materials may be edited for content and length.


Cite This Page:

University Of California San Francisco. "UCSF Team Identifies Two Key Molecules In Asthma -- Important Finding For New Therapies That Treat Disease At Cell Level." ScienceDaily. ScienceDaily, 18 December 1998. <www.sciencedaily.com/releases/1998/12/981218075909.htm>.
University Of California San Francisco. (1998, December 18). UCSF Team Identifies Two Key Molecules In Asthma -- Important Finding For New Therapies That Treat Disease At Cell Level. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/1998/12/981218075909.htm
University Of California San Francisco. "UCSF Team Identifies Two Key Molecules In Asthma -- Important Finding For New Therapies That Treat Disease At Cell Level." ScienceDaily. www.sciencedaily.com/releases/1998/12/981218075909.htm (accessed July 25, 2014).

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