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EGF receptor found to regulate macrophage inflammation in gut

Keith Wilson, M.D., Dana Hardbower and colleagues are studying the link between epidermal growth factor receptor (EGFR) signaling and the inflammatory response to bacterial infection in the gastrointestinal tract. (photo by Steve Green)

Researchers at Vanderbilt University School of Medicine have uncovered a link between epidermal growth factor receptor (EGFR) signaling and the inflammatory response to bacterial infection in the gastrointestinal tract.

In particular, they have found — in mice and human tissue — that EGFR signaling regulates the response of an inflammatory macrophage (a type of white blood cell) to infection by the ubiquitous intestinal bacterium H. pylori and in a mouse model of infectious colitis.

Their findings, published in the September issue of the Journal of Clinical Investigation and selected as one of the “editor’s picks” by the journal, suggest that currently available drugs which block the EGFR signaling could be useful in treating or preventing chronic inflammation in the gut associated with infection.

Since chronic inflammation increases the risk for gastric cancer, these drugs might also reduce cancer risk as well, said first author Dana Hardbower, a graduate student in Microbiology and Immunology who led the study with senior author Keith Wilson, M.D.

Wilson, the Thomas F. Frist Sr. Professor of Medicine and professor of Cancer Biology and of Pathology, Microbiology and Immunology, is director of Research in the Division of Gastroenterology and founding director of the new Center for Mucosal Inflammation and Cancer at Vanderbilt University Medical Center.

“Inflammation as a driver of carcinogenesis is a huge topic now,” Hardbower said. “Cancers of the GI tract especially are driven by chronic inflammation.” Understanding the role of EGFR signaling in macrophage activation thus could potentially be important in improving treatment of other inflammatory diseases of the gut, she said.

Half the world’s population is infected by H. pylori. While only 1 to 3 percent of infected people develop gastric cancer, the sheer number is enormous. That’s one reason why gastric cancer is the third leading cause of cancer death worldwide, after lung and liver cancer.

Twenty years ago, Wilson was the first to show a connection between H. pylori infection and macrophage activation. This initial work has led to a series of studies focused on understanding immune dysregulation and how the associated inflammation can lead to cancer.

In 2015, Hardbower was awarded a two-year grant, No. DK107159, from the National Institutes of Health (NIH) to support the study, which was her dissertation research project. Earlier this year she received the annual Sidney P. Colowick Graduate Student Award in Microbiology and Immunology, primarily for this work.

The research also was supported by five NIH grants to Wilson — DK053620, AT004821, CA190612, CA116087 and CA028842 — and by Department of Veterans Affairs Merit Review grant I01BX001453.