What If You Could Flip a Switch to Breathe Easier?

Cellular “off” switch for inflammatory immune response discovered by Johns Hopkins researchers.

diagram of health and asthmatic airwaysIf you’ve ever had an asthma attack, you know how terrifying it can be. Some asthmatics compare those attacks to trying to breathe through a straw. What if asthma attacks could simply be switched off? Researchers say it’s possible.

According to a press release issued by Johns Hopkins Medicine, researchers at the university have discovered a cellular “off” switch for the inflammatory immune response that triggers lung-constricting asthma attacks. The switch is composed of regulatory proteins that control an immune signaling pathway in cells.

“Asthma patients are constantly firing through this pathway because those proteins are stuck in the on position, without proper control by other proteins that shut down this reaction,” lead researcher Nicola Heller, PhD, said in the press release.

Dr. Heller is an assistant professor of anesthesiology and critical care medicine at the Johns Hopkins University School of Medicine.

About 17.7 million adults and 6.3 million children in the US have asthma, according to the Centers for Disease Control and Prevention (CDC). Asthma is a lung disease that can cause wheezing, breathlessness, chest tightness and coughing and is often controlled by taking medicine and avoiding environmental triggers.

Previous research linked asthma to one type of immune cell called M2 macrophages in the lungs. In non-asthmatic people, M2 activates to clean up allergens and foreign particles. In asthmatics, M2 cells’ chemical signal lingers and calls in other cells that cause inflammation.

This study focused on two proteins, GRB10 and p70S6K, that control the signaling pathway that activates M2.

To conduct the study, researchers analyzed cultures of human white blood cells. They found that the IRS-2 pathway, which chemicals pass through before activating M2, appeared in two different forms—“on,” which allowed signals to pass through, and “off,” which stopped signals from activating M2.

They found the activity of the regulatory proteins GRB10 and p70S6K increased after exposure to IL-4, an immune system chemical that passes through IRS-4 on its way to M2 cells.

Researchers treated the white blood cells with chemical and genetic blockers designed to render GRB10 and p70S6K nonfunctional. They found that decreasing the two proteins’ activity resulted in more of the “on” form of IRS-2, suggesting that the proteins are responsible for turning off IRS-2 and downstream M2 production.

“This confirmed for us that without properly functioning GRB10 and p70S6K, the cells could not turn off IRS-2 signaling and M2 production,” Dr. Heller said in the press release.

Researchers said they’ve already started experiments to understand the implications of their findings. They hope their research will have applications for cancer and obesity treatment in which M2 macrophage cells play a regulatory role in tumor growth and fat deposition.

The full study was published in the Journal of Biological Chemistry.

It was funded by the National Institutes of Health Pathway to Independence Award.

The authors declared no conflicts of interest.

Sources:
Johns Hopkins Medicine, “Turning Off Asthma Attacks”
https://www.eurekalert.org/pub_releases/2016-12/jhm-toa120116.php
CDC, “Asthma”
https://www.cdc.gov/asthma/
Journal of Biological Chemistry, “The TORC1-activated proteins, p70S6K and GRB10, regulate IL-4 signaling and M2 macrophage polarization by modulating phosphorylation of insulin receptor substrate-2”
http://www.jbc.org/content/291/48/24922.full?sid=f1afcdda-2362-4313-9fba-1b55ee149c16
Written by: Beth Greenwood, RN | Medically reviewed by: Dr. Robert Carlson, M.D.