08:12am Thursday 17 August 2017

Discovery of New Signaling Intermediates Provides Clues to Novel Therapies in Pancreatitis

“A network of intercellular signals involving pancreatic acinar cells, nerves and immune cells results in progression of pancreatitis,” said lead study author Rafiq A. Shahid, MD, from Duke University. “We made an exciting discovery that leukotriene B4 is synthesized and released by acinar cells and, in turn, activates sensory nerves to trigger pain and inflammation in acute pancreatitis. If we can develop a treatment that blocks leukotriene B4, we would then be able to limit both pain and inflammation in patients suffering from this disease.”

Using a mouse model, researchers explored the previous finding that transient receptor potential vanilloid-1 (TRPV1) receptors on sensory nerves are involved in development of pain and inflammation in pancreatitis. The activation of TRPV1 receptors plays a vital role in the early stages of development of pancreatitis, so the researchers questioned how these receptors are activated. They found that leukotriene B4 plays a pivotal role in this process. 

The results also demonstrate that targeting leukotriene B4 by inhibiting 5-lipoxygenase, which is a key enzyme required for leukotriene B4 synthesis, is beneficial in experimental chronic pancreatitis. This provides an avenue for development and clinical evaluation of 5-lipoxygenase inhibitors for patients with pancreatitis.

“This discovery of previously unknown signaling pathways may lead to new therapeutic opportunities in pancreatitis,” said Jerrold Turner, MD, PhD, AGAF, editor-in-chief of Cellular and Molecular Gastroenterology and Hepatology. “We are pleased to feature this ground-breaking research in the inaugural issue of the journal.”

Pancreatitis is a common disorder that complicates many ailments, including cystic fibrosis and alcoholism. Few therapies exist, and management of the severe pain associated with inflammation is a major obstacle that often requires strong narcotics. However, narcotic use can be dangerous and often adds to the problems of patients with pancreatitis. Learn more about pancreatitis in the AGA patient brochure.

The authors have no conflicts to disclose.

AGA announced the launch of Cellular and Molecular Gastroenterology and Hepatology in November 2014. This study appears in the inaugural issue of the journal.

1Shahid, Rafiq A. et al., Acinar Cell Production of Leukotriene B4 Contributes to Development of Neurogenic Pancreatitis in Mice, Cellular and Molecular Gastroenterology and Hepatology 2015: 1(1): 75-68, http://www.cmghjournal.org/article/S2352-345X(14)00006-X/abstract

About the AGA Institute 

The American Gastroenterological Association is the trusted voice of the GI community. Founded in 1897, the AGA has grown to more than 16,000 members from around the globe who are involved in all aspects of the science, practice and advancement of gastroenterology. The AGA Institute administers the practice, research and educational programs of the organization. www.gastro.org

About Cellular and Molecular Gastroenterology and Hepatology

CMGH is the newest peer-reviewed journal published by the American Gastroenterological Association (AGA). The mission of CMGH is to publish impactful digestive biology research that ranges from mechanisms of normal function to pathobiology and covers a broad spectrum of themes in gastroenterology, hepatology and pancreatology. The journal reports the latest advances in cell biology, immunology, physiology, microbiology, genetics and neurobiology of gastrointestinal, hepatobiliary, and pancreatic health and disease. For more information, visit www.cmghjournal.org.


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