(Press-News.org) Contact information: Susan Gammon
858-795-5012
Sanford-Burnham Medical Research Institute
Discovering a 'THRIL' that correlates with severity of Kawasaki disease
LA JOLLA, Calif., December 26, 2013 – Sanford-Burnham Medical Research Institute scientists have discovered a new molecule that forms when certain white blood cells—macrophages—are stimulated in response to pathogens. The molecule, termed "THRIL," helps regulate the immune response and shows an association with Kawasaki disease. The findings suggest that THRIL may contribute to other inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease.
The study, published online in Proceedings of the National Academy of Sciences, measured large intergenic noncoding RNA (lincRNA) produced when the immune system is activated. One lincRNA was found to bind heterogenous nuclear ribonucleoprotein L (hnRNPL), creating a new molecule that regulates genetic control of TNF-alpha—a potent cytokine that promotes inflammation. The authors named the molecule THRIL, after TNF-alpha and hnRNPL-related immunoregulatory lincRNA.
Noncoding RNAs as key regulators of immune response
Large noncoding RNA corresponds to the parts of the genome that do not code for protein.
"For some time we have known that noncoding regions of RNA play important roles in regulating the immune response to microbial pathogens," said Tariq Rana, Ph.D., senior author of the study and professor in the Sanford Children's Health Research Center and director of the RNA Biology Program at Sanford-Burnham. "When we realized that THRIL functioned to control the TNF-alpha gene, we wanted to see if it mirrors the progression in inflammatory diseases."
Collaborating with Jane Burns, M.D., professor of pediatrics at Rady Children's Hospital and UC San Diego, Rana's team measured THRIL levels in Kawasaki disease samples at different stages of the disease, and found that levels were at their lowest during the acute stage of the disease—when TNF-alpha levels are at their highest.
The findings suggest that THRIL could be a novel biomarker for immune activation and a potential target for inflammatory diseases.
INFORMATION:
This research was funded in part by the National Institutes of Health grants AI41404, AI43198, and DA30199, and Integrating Data for Analysis, Anonymization, and Sharing grant U54HL108460.
The study was co-authored by Zhonghan Li, Sanford-Burnham Medical Research Institute; Ti chun Chao, Sanford-Burnham Medical Research Institute; Kung-Yen Chang, Sanford-Burnham Medical Research Institute; Nianwei Lin, Sanford-Burnham Medical Research Institute; Veena Patil, Sanford-Burnham Medical Research Institute; Chisato Shimizu, Department of Pediatrics, Rady Children's Hospital San Diego and UC San Diego; Steven R. Head, The Scripps Research Institute; Jane C. Burns, Department of Pediatrics, Rady Children's Hospital San Diego and UC San Diego; and Tariq M. Rana, Sanford-Burnham Medical Research Institute and UC San Diego.
About TNF-alpha
TNF-alpha is a signaling protein produced mainly by macrophages in the body's response to infection. TNF-alpha is known to drive inflammation and tissue destruction in immune mediated diseases. Anti-TNF drugs are used to control inflammatory diseases such rheumatoid arthritis and psoriasis.
About Macrophages
Macrophages are the first line of defense for the immune system, and are considered to be the "bottom feeders" of white blood cells. They work by ingesting many cells and depending on the type of cell ingested they send signals—such as TNF-alpha—to alert the rest of the immune system that it's time to defend the body.
About Kawasaki Disease
Kawasaki disease is a rare childhood disease that involves inflammation of the blood vessels. In some cases, the disease affects the coronary arteries, leading to serious heart problems. Kawasaki disease affects children of all races, genders, and ages. It occurs most often in children of Asian and Pacific Island descent. Symptoms include red eyes, red lips, and redness on the palm of their hands and soles of their feet—all signs of inflamed blood vessels.
The cause of the disease is unknown, and it can't be prevented. Although the disease has a good prognosis with treatment, it can lead to death from coronary artery aneurysm in a small percentage of patients.
About Sanford-Burnham Medical Research Institute
Sanford-Burnham Medical Research Institute is dedicated to discovering the fundamental molecular causes of diseases and devising the innovative therapies of tomorrow. Sanford-Burnham takes a collaborative approach to medical research with major programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory and childhood diseases. The Institute is recognized for its National Cancer Institute-designated Cancer Center and expertise in drug discovery and stem-cell technologies. Sanford-Burnham is a nonprofit, independent institute that employs 1,200 scientists and staff in San Diego (La Jolla), Calif., and Orlando (Lake Nona), Fla. For more information, visit us at http://www.sanfordburnham.org.
Discovering a 'THRIL' that correlates with severity of Kawasaki disease
2013-12-27
ELSE PRESS RELEASES FROM THIS DATE:
Who is using MyPlate?
2013-12-27
Who is using MyPlate?
Food preferences, cooking ability, involvement of children in food preparation, nutritional knowledge, and prior familiarity with MyPyramid were predictors of MyPlate awareness and use
Most Americans know about MyPyramid – the triangle ...
BU researchers explore possible link between cognitive depressive symptoms and antiretroviral therapy uptake
2013-12-21
BU researchers explore possible link between cognitive depressive symptoms and antiretroviral therapy uptake
Researchers from Boston University's School of Medicine (BUSM) and College of Arts and Sciences (CAS) found that among HIV-infected Russian drinkers, ...
Wayne State University physicists publish observation of the 'Charming Socialites'
2013-12-21
Wayne State University physicists publish observation of the 'Charming Socialites'
DETROIT — Protons and neutrons, the particles in an atomic nucleus, are made of smaller pieces called "quarks." Some types of quarks ...
Starless cloud cores reveal why some stars are bigger than others
2013-12-21
Starless cloud cores reveal why some stars are bigger than others
Massive stars – those at least 8 times the mass of our Sun – present an intriguing mystery: how do they grow so large when the vast majority of stars in the Milky Way are considerably smaller?
To ...
Researchers find potential new treatment approach for pancreatic cancer
2013-12-21
Researchers find potential new treatment approach for pancreatic cancer
Scientists from The University of Manchester -- part of Manchester Cancer Research Centre believe they have discovered a new way to make chemotherapy treatment more effective ...
Wayne State cholesterol study shows algal extracts may counter effects of high fat diets
2013-12-21
Wayne State cholesterol study shows algal extracts may counter effects of high fat diets
Health Enhancement Products, Inc. (OTC.BB:HEPI.OB – News), in conjunction with Wayne State University's Department of Nutrition ...
Staph stoppers
2013-12-21
Staph stoppers
New vaccine from University of Iowa protects against lethal pneumonia caused by staph bacteria
University of Iowa researchers have developed a new vaccine that protects against lethal pneumonia caused by Staphylococcus aureus (staph) bacteria, including ...
A wrong molecular turn leads down the path to Type 2 diabetes
2013-12-21
A wrong molecular turn leads down the path to Type 2 diabetes
Computing resources at the U.S. Department of Energy's (DOE) Argonne National Laboratory have helped researchers better grasp how proteins misfold to create the tissue-damaging structures that ...
UNL research raises concerns about global crop projections
2013-12-21
UNL research raises concerns about global crop projections
30 percent of world's corn, rice and wheat crop land may be 'maxed out'
LINCOLN, Neb. — About 30 percent of the major global cereal crops – rice, wheat and corn – may have reached their maximum possible ...
Penn researchers grow liquid crystal 'flowers' that can be used as lenses
2013-12-21
Penn researchers grow liquid crystal 'flowers' that can be used as lenses
A team of material scientists, chemical engineers and physicists from the University of Pennsylvania has made another advance in their effort to use liquid crystals as a medium for assembling ...