Major Events in Immune System Linked to Bowel Disease

Researchers at Virginia Bioinformatics Institute pointed out that important molecular events in the immune system of a person contributes to inflammatory bowel disease.

The results will help researchers move one step further in their efforts to develop new drugs to treat inflammatory and immune-mediated diseases.

Crohn’s Disease
Crohn’s disease or regional enteritis is an inflammatory bowel disease that involves the small intestine and causes abdominal pain, diarrhea and bleeding.

Inflammatory bowel disease starts when the gut initiates an abnormal immune response to some of the one hundred trillion or so bacteria that come into contact with the colon of the human body.

The immune cells identified in the earlier work, which are known as M1 or classically activated macrophages, cause inflammation and possess a specific molecule, peroxisome proliferator-activated receptor-gamma, that, when activated, favors a switch to a type of macrophage that reduces the impact of inflammation (alternatively activated macrophage or M2).he activation of the receptor protein and the anti-inflammatory M2 macrophage switch plays a beneficial role in reducing the severity of the disease in the gut during experimentally induced inflammatory bowel disease.

"We have been able to validate experimentally some of the key events that take place in the regulation of the mucosal immune system when inflammatory bowel disease is triggered in mice," said Josep Bassaganya-Riera, associate professor of immunology at the Virginia Bioinformatics Institute, leader of the Nutritional Immunology and Molecular Medicine Group in the institute's CyberInfrastructure Division.

Ulcerative Colitis
Ulcerative colitis is characterized by bouts of diarrhea, bleeding per rectum and pain, which remits and relapses. Fulminant colitis is a possibility, which may require colectomy.

"When we produce mice that lack the peroxisome proliferator-activated receptor-gamma specifically found in macrophages, the severity of inflammatory bowel disease increases significantly. In parallel, we are able to observe the impact of the onset of disease on key inflammation-related genes and other molecules involved in inflammation and metabolism."

"In this study, we were able to use mouse Affymetrix GeneChips(r) to examine which genes were turned on and off under disease and non-disease conditions," said Clive Evans, director of the Core Laboratory Facility at the institute.

Spinal Arthritis and Inflammatory Bowel Disease Connected Genetically
A form of spinal arthritis, researchers at the University of Queensland Diamantina Institute in Brisbane, Australia have discovered, is genetically linked to Inflammatory Bowel Disease.

"This gave us a comprehensive snap-shot of what is happening in the immune system of mice when inflammation-related disease takes hold in the gut."

"In addition to our observations of what is happening when inflammatory bowel disease is triggered in mice, we showed that peroxisome proliferator-activated receptor-gamma in macrophages is essential for recovery from disease when the drug pioglitazone is used to treat it," said Raquel Hontecillas, assistant professor of immunology at the Virginia Bioinformatics Institute, and lead investigator of the study.

Post Traumatic Stress Caused by Inflammatory Bowel Disease
Inflammatory bowel disorder, Crohn's disease, is the cause of a variant of post traumatic stress (PTSD), claims a new research study.

"Our group has dissected the role of peroxisome proliferator-activated receptor-gamma as an internal thermostat for inflammation in other cells involved in gut inflammation such as intestinal epithelial cells and T cells."

The researchers hope to use their knowledge of the immune system and specific targets for re-purposed drugs and naturally occurring compounds to develop safer alternatives for the long-term management of the disease.

"Our combined computer modeling and experimental validation approach, which is part of the work of our Center for Modeling Immunity to Enteric Pathogens, is already generating important clinical leads that should help us in our quest to deliver better therapies for infectious enteric diseases," concluded Bassaganya-Riera.

The results are reported in the November 2010 edition of the journal Mucosal Immunology.

Source-ANI