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Fluorescence in situ hybridization (FISH) localization of human LITAF gene

New Promise for Controlling Crohn's and Other Inflammatory Diseases

A new gene involved in common inflammatory diseases, like rheumatoid arthritis and Crohn's disease, was recently discovered by scientists at Boston University's School of Dental Medicine.

The scientists identified the gene that controls production of Tumor Necrosis Factor alpha (or TNF), a molecule the body produces when it needs to destroy unwanted tissues - when it is fighting infection, for example. The researchers believe that this molecule is also implicated in a wide variety of inflammatory diseases - diseases in which the body literally attacks itself - including periodontal disease, septic shock, rheumatoid arthritis, lupus, Crohn's disease, and diabetes.

"We believe this discovery offers new insights into how the body regulates the fundamental pathway involved in inflammation and opens up new ways to find and to treat currently untreatable diseases, " explains Dr. Salomon Amar, Associate Professor of Oral Biology and Periodontology at Boston University's School of Dental Medicine. Amar led a team of four researchers at the Boston University School of Dental Medicine and School of Medicine.

The scientists deleted portions of the promoter of the TNF gene and tested whether or not the gene continued to function. They found that if a particular sequence were removed, cells could not produce TNF. Further, they found that this sequence bound a previously unknown transcription factor - a molecule that regulates other molecules like TNF that exert a powerful effect on the body. They named this molecule LITAF (lipopolysaccharide-induced transcription factor).

Two different pharmaceutical companies are currently developing anti-TNF therapies for Crohn's disease. However, both protein molecules under development are too expensive and too difficult to administer to be ideal for the long-term therapy necessary for chronic conditions like Crohn's disease. The Boston University discovery will utilize LITAF to produce small molecule therapeutics which can be more easily and economically used to treat chronic inflammatory conditions like Crohn's disease.

The research leading to this discovery was supported by the National Institute of Craniofacial and Dental Research of the National Institutes of Health. It was reported in the Proceedings of the National Academy of Sciences (Vol. 96).

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29 April 1999
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