Immune system protein could explain pancreatitis

The research results have been published in the American journal Gastroenterology.

Excessive alcohol intake and gall stones are known risk factors for acute pancreatitis. However, as yet no explanation has been found for what actually happens in the body in cases of acute pancreatitis.

Current research shows that calcium-sensitive proteins found in the body, for example calcineurin, promote inflammation, but it is not known exactly how.

Henrik Thorlacius and Maria Gomez at the University’s Department of Clinical Sciences in Malmö have investigated this in more detail. The focus is on a family of proteins linked to calcineurin, called NFAT, the role of which in acute pancreatitis has not previously been studied.

“The protein has an unexpectedly major role in the development of inflammation in the pancreas. Now there is a clear target for the development of drugs and treatments”, says Henrik Thorlacius, Professor of Surgery at Lund University and a doctor at Skåne University Hospital.

In experiments on mice, the researchers found a number of links between NFAT and acute pancreatitis. NFAT, and especially the variant NFATc3, were found to regulate the activity of trypsinogen (a precursor form of the digestive enzyme trypsin), which can affect the risk of acute pancreatitis. The activation of NFATc3 was also found to encourage inflammation and tissue damage in the pancreas in various other ways.

“In our study, we saw that the aorta, spleen and lungs were also affected. The results therefore suggest that the NFAT protein plays a part in the development of inflammatory diseases on a more general level”, says Henrik Thorlacius.

The findings open up new opportunities for research on treatment and drugs, both for acute pancreatitis and for other acute inflammatory diseases, such as blood poisoning and inflammatory bowel disease.

“An effective drug needs to contain a substance that stops the activation of NFATc3 without producing serious side-effects”, says Professor Thorlacius.

The NFAT proteins function as transcription factors, which means that they can be bound to the body’s DNA and regulate the expression of specific genes in different cells. They have so far primarily been associated with immune cells.

Publication
Article title: ‘NFATc3 Regulates Trypsinogen Activation, Neutrophil Recruitment, and Tissue Damage in Acute Pancreatitis in Mice’

Published in: Gastroenterology

About acute pancreatitis
The pancreas forms various enzymes and hormones that are necessary for digestion and to keep sugar levels stable.

Pancreatitis can be either chronic or acute, and as yet no one has been able to explain the causes of the disease. High alcohol intake and gall stones are known risk factors.

Every year, one person in 1 000 in Sweden is affected by pancreatitis, corresponding to around 9 000 cases. Of these, 10–20 per cent fall seriously ill, with a risk of fatality. There are no effective drugs to treat the condition.

For more information
Henrik Thorlacius, Professor of Surgery at the Department of Clinical Sciences in Malmö, Lund University and doctor at Skåne University Hospital, +46 70 34 55 150, henrik.thorlacius@med.lu.se

Maria F. Gomez, Reader in Physiology at the Department of Clinical Sciences in Malmö, Lund University, +46 70 222 62 16, maria.gomez@med.lu.se