Study Finds Molecule Behind Diverse Human Chronic Inflammatory Diseases

by Rajashri on Sep 17 2008 5:11 PM

A common connection between the cellular innate immunity network and chronic inflammatory diseases like atherosclerosis, Type 2 Diabetes, and neurodegenerative diseases has been uncovered by Virginia Tech researchers.

Research leader Liwu Li, an associate professor of Biological Sciences, says that the new finding offers a viable cellular and molecular target for the diagnosis and treatment of serious human inflammatory diseases.

"Researchers and physicians have long recognized that there is an association between these conditions. For example, obesity increases the risk of heart attack or stroke, Type 2 Diabetes or insulin resistance, and Alzheimer's Disease," said Li, who is the founding director of the Inflammation Center at Virginia Tech.

"Inflammation is the common mechanism. Inflammation is a double-edged sword. Proper inflammation is necessary to fend off infection and abnormal cell growth. On the other hand, excessive inflammation contributes to diverse chronic diseases, including atherosclerosis, diabetes, and lupus," he added.

The researcher, however, admitted that the research team were yet to understand the complex cellular and molecular networks controlling inflammation properly.

"The lack of understanding impedes our progress in treating serious chronic inflammatory diseases," he said.

For their research, the researchers studied transgenic mice that lacked a key cellular protein kinase named interlukin-1 receptor associated kinase 1 (IRAK-1), previously shown to be critical for processing diverse inflammatory signals.

Li and his colleagues found that IRAK-1 deficient mice were protected from developing atherosclerosis and insulin resistance.

The researchers also found that IRAK-1 prefers to phosphorylate transcription factors harbouring the Serine-Proline motif including STAT-3 and NFAT, which are involved in modulating the expression of distinct inflammatory mediators responsible for the excessive activation of specialized macrophages and T cells.

The cells eventually contribute to diverse inflammatory symptoms including cardiovascular diseases, diabetes, Alzheimer's diseases, and lupus.

"Chemical compounds targeting this molecule will have enormous therapeutic potential," Li said.

"There is still a long way to go for finding the actual cure for these diseases. That is why we are combining expertise from various disciplines, including experimental biology and computational simulation. The Inflammation Center integrates faculties with expertise in experimental molecular biology, cutting edge imaging of inflamed cells and tissues, computational simulation of cellular signaling networks, human and animal studies, and nano-technologies designing novel intervention," he said.

Virginia Tech Intellectual Properties Inc. (VTIP) filed a patent application for Li's discovery, and its use as a diagnostic tool and treatment strategy.

"This technology will still take some time before there is a product," said Li.