Three potent proteins of the immune system, evolved to purge us of intestinal parasites, now often launch misguided attacks in our airways, triggering the congestion of asthma that leaves millions gasping for air.
By studying the genetic machinery that controls production of these immune soldiers called cytokines, a team of scientists has demonstrated a potential strategy to silence their misfiring and quell the asthma response.
In back-to-back papers in April and May, researchers at UC San Francisco and the Lawrence Berkeley National Laboratory (LBL) report that a stretch of DNA controlling all three cytokine genes is so similar in humans and mice that the mouse DNA can activate the three human genes inserted in a mouse.
The researchers showed too that the activity of all three genes can be at least partially blocked, suggesting that a single drug could be used to attack asthma at its genetic source. Such a drug could be reliably tested in mice, their study shows.
"The primary aim of our research has been to demonstrate that if non-coding regions of DNA (stretches containing no genes) have been conserved in species separated by many millions of years, they probably perform vital functions," said Richard Locksley, MD, investigator in the Howard Hughes Medical Institute and professor of medicine and microbiology/ immunology at UCSF.
"But in choosing a DNA region that modulates the genes for the cytokines IL-4, 5 and 13, we are dealing with genes that are dramatically expressed in asthma and other allergic diseases. Our experiments show that all three genes are regulated by the same non-coding DNA region, and interruption of this control affects all three genes at once. By blocking the activity of this region, we should be able to block the expression of all three genes."
Many drugs are now being designed to interfere with activity of a single gene or the protein coded by that gene, but developing a drug to treat a disease caused b
Contact: Wallace Ravven
University of California - San Francisco