Molecular Researchers Find New Key to Inflammatory Diseases

Biologists have discovered genetic material that may help to explain part of how our immune defense is triggered. Dubbing it THRIL, they say it could be targeted in the development of treatments against inflammatory diseases such as Kawasaki disease, rheumatoid arthritis and inflammatory bowel disease.

The researchers have discovered a new molecule that forms when the immune response is triggered by pathogens - disease-causing bacteria and viruses. The THRIL molecule, they found, is involved when white blood cells called macrophages are stimulated as part of the cascade of immunity that defends the body. The molecule, say the scientists from San Diego, CA, and Ontario, Canada, helps regulate the immune response and shows an association with Kawasaki disease, the immune disorder that the medical researchers focused on for their study - a rare childhood disease that involves inflammation of the blood vessels. The lead study author, Tariq Rana, PhD, is from the Sanford-Burnham Medical Research Institute in Ontario, which also has a base in Orlando, FL. He says the work builds on the knowledge of RNA genetic material and its role in our innate response to microbial threats. Dr. Rana, who is a professor in the Sanford Children's Health Research Center and director of the RNA Biology Program at Sanford-Burnham, says: "For some time we have known that noncoding regions of RNA play important roles in regulating the immune response to microbial pathogens." He adds: "When we realized that THRIL functioned to control the TNF-alpha gene, we wanted to see if it mirrors the progression in inflammatory diseases."

The research paper introduces TNF-alpha as "a critical cytokine released early in the innate immune response." In other words, it promotes inflammation. So a molecule that affects TNF-alpha levels may be important to the understanding of inflammatory disease. Molecular research on immune responses in children with inflammatory disease Dr. Rana's research team measured THRIL levels in samples taken from children with different stages of Kawasaki disease. Collaborating with clinician Dr. Jane Burns - a professor of pediatrics at the University of California and the Rady Children's Hospital in San Diego, CA - the team found that the THRIL levels were lowest during the acute stage of the disease, when TNF-alpha levels are at their highest. The researchers conclude: "The findings suggest that THRIL could be a novel biomarker for immune activation and a potential target for inflammatory diseases." Summarizing the significance of their research, the authors say in the scientific paper that the new molecule plays an important role in healthy (physiological) inflammatory immune responses as well as being involved with pathological responses. SOURCE: The study is published online in the Proceedings of the National Academy of Sciences. The authors named the molecule THRIL after "TNF-alpha- and hnRNPL-related immunoregulatory lincRNA."