Scientists at NIEHS have identified a protein which may help in the quest for drugs to fight inflammatory diseases including rheumatoid arthritis, Crohn's disease, physical wasting, and graft-versus-host disease. The protein may help counteract the ill effects when the body produces excessive amounts of another protein key to fighting infection.
In proper balance, a bodily protein called tumor necrosis factor alpha performs like a hero, helping to fight infections and other bodily invaders. But like a hero gone awry, excessive TNF production stimulated by TNF itself can cause a host of inflammatory ills, such as those mentioned above, and the physical wasting that accompanies many cancers and AIDS.
Now, however, scientists at the National Institute of Environmental Health Sciences have identified a protein that can put the brakes on TNF.
Using genetically modified mice with a specific gene removed, researchers at the National Institute of Environmental Health Sciences have identified a protein that counters TNF, that in turn may lead to drugs that will curb TNF's ravages. This protein is called Tristetraprolin, or TTP.
In previous experiments, the researchers found that mice genetically modified to remove the TTP gene suffer many ailments similar to those associated with overproduction of TNF in people; yet when TNF is controlled in the mice, most of the TNF-induced problems do not develop. In their new study, published in Science (Vol. 281, p. 1001), the researchers found that this overproduction of TNF in the TTP deficient mice was due to the absence of TTP's controlling effect on TNF's synthesis by inflammatory cells.
Authors of the study are Ester Carballo, M.D., Ph.D., and Wi S. Lai, Ph.D., both of the Laboratory of Signal Transduction, NIEHS, and Perry J. Blackshear, M.D., D.Phil., Director of Clinical Research, NIEHS.
Dr. Blackshear said that TTP appears to regulate production
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Contact: Tom Hawkins
hawkins@niehs.nih.gov
(919) 541-1402
NIH/National Institute of Environmental Health Sciences
9-Sep-1998