Researchers from the Johns Hopkins University School of Medicine have discovered a cellular "off" switch to deactivate the compounds that cause a severe inflammatory response, which results in asthma attacks.

According to Nicola Heller from Johns Hopkins, asthma patients experience debilitating symptoms because of the consistent activity of the proteins that are not switched "off" by regulatory proteins responsible for the inflammatory reactions.

Asthma Inflammatory Pathway

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.

As a result of such continuous attacks the lungs get remodeled over time, resulting in irreversible obstruction and deterioration in lung functions. If the activity of M2 macrophages are brought under control, the inflammatory responses and other related consequences could be contained, noted Heller.

Proteins Involved In Inflammatory Response

The investigators 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.

For their latest research, the researchers took a closer look at 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.

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

New Asthma Treatment Option

Following the discovery, the researchers started exploring the differences in the inflammatory pathways of healthy and asthmatic individuals and the role of the inhalable drugs that work similarly to GRB1 and p70S6K, which could shut down M2 cells.

Heller noted that the inhalable drugs are more likely to work since the lung macrophages are the cells that are first exposed to the inhalers.

The study is published in the Journal of Biological Chemistry.

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