Penn Dental Medicine Study Shows Where a Protein is Expressed Can Influence its Action

News provided by

Dec 21, 2018, 08:48 ET

PHILADELPHIA, Dec. 21, 2018 /PRNewswire/ -- Health conditions that involve inflammation run the gamut, from multiple sclerosis and lupus to arthritis, diabetes, and cancer. While inflammation can serve as a normal response to help the body deal with injury or infection, problems arise when it persists, potentially harming surrounding tissues.

To prevent or ameliorate this damage, the body relies on a strategy to actively clear inflammation. "It's not just extinguishing the fire of inflammation," says Dr. George Hajishengallis, Thomas W. Evans Centennial Professor of Microbiology at Penn Dental Medicine. "You also have to return things to the way they were before the inflammatory destruction."

A new study led by Hajishengallis and Triantafyllos Chavakis of the Technical University of Dresden has illuminated a key player in this resolution process—the protein Del-1, which the pair has studied extensively before. While prior research had underscored Del-1's role in curbing the initiation of inflammation, the new work finds that it can also serve a very different function, actively working to clear inflammation. Which function the protein performs depends on the cell type that expresses it, the team found. The work has appeared in the journal Nature Immunology.

In their earlier studies, Hajishengallis and Triantafyllos Chavakis had found Del-1 secreted from endothelial cells that line tissues was responsible for regulating initiation of inflammation by inhibiting the traffic of neutrophils. But their new work has shown that macrophages, too, could secrete Del-1. Using mice that overexpressed either the endothelial-derived Del-1 or the macrophage-derived Del-1, they found that the cell type mattered when it came to the protein's activity. Overexpressing Del-1 only in endothelial cells, for example, made no difference in the animals' ability to clear dying neutrophils from the area of inflammation. Conversely, mice overexpressing Del-1 in their macrophages had no advantage in harnessing neutrophil recruitment but were better able to clear the neutrophils from the site of inflammation.

"This 'location principle' is novel," says Hajishengallis. "Tissues are not a sack of molecules; the geography is very important."

The work was supported by grants from the European Research Council, the Deutsche Forschungsgemeinschaft, the National Institutes of Health (grants AI068730, DE024153, DE024716, DE026152, and DE015254) and the NIH intramural research program of the National Institute of Dental and Craniofacial Research.

CONTACT: Beth Adams, [email protected], 215-573-8224

SOURCE Penn Dental Medicine