Giving a huge relief to the asthma patients, a new study has revealed ways of switching off the painful asthma attacks.
Working with the human immune cells in the laboratory, researchers from the Johns Hopkins University School of Medicine have discovered a critical cellular ‘off’ switch to deactivate the compounds that cause a severe inflammatory response, which results in asthma attacks.
Assistant professor of anesthesiology and critical care medicine from John Hopkins Nicola Heller (PHD) said the switch is composed of regulatory proteins that control an immune signaling pathway in cells. In his opinion, “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.”
The new study was published on the Journal of Biological Chemistry.
In healthy individuals the M2 macrophages that are activated as a result of immune response clean up allergens in the lungs and get deactivated after the process. However, in asthmatic patients the M2 macrophages linger and signal other inflammatory cells, causing an asthma attack with symptoms such as shortness of breath, breathing difficulty and wheezing.
Over time, the lung is changed by secretions from the M2 cells, which cause the lung tissue to remodel itself, contributing to irreversible obstruction and poor lung function. “If you prevent these cells from becoming the M2 type, you can potentially stop the continued inflammation and long-term structural changes,” says Heller.
The researchers analyzed the role of two important proteins, GRB10 and p70S6K that are responsible for activating M2 macrophages.
Heller’s team noted in a previous study that the M2 cells are activated after interleukin 4 (IL-4), a chemical compound, passes through the protein IRS-2. They found that the proteins that control and terminate the activity of IRS-2 were absent in the M2 cells of asthmatic patients.
In the new study, Heller’s lab delved deeper into the IRS-2 pathway. By conducting tests on immortalized cultures of human white blood cells, they found that the activity of the regulatory proteins GRB10 and p70S6K determines whether IRS-2 will be turned on “on” or “off”.
When the white blood cells were treated with small interfering RNA (siRNA) that is designed to deactivate GRB10 or p70S6K, it was found that a reduction in the protein activity turned on the IRS-2.
The research team, Heller says, has already begun experiments to further explore the implications of these results, which include looking at differences in this pathway between cells taken from allergic and healthy individuals, and testing the efficacy of an inhalable drug that mimics the function of GRB1 and p70S6K to shut off the development of M2 macrophages in the lungs of mice.
