Increase in TTP protein protects against inflammatory diseases

John Murphy, MDLinx | February 05, 2016

Mice that produced higher levels of the protein tristetraprolin (TTP) were more resistant to certain damaging inflammatory diseases—including rheumatoid arthritis, psoriasis, and multiple sclerosis, according to an article published online February 1, 2016 in the Proceedings of the National Academy of Sciences.

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Treatment for inflammation of rheumatoid arthritis

In a model of rheumatoid arthritis, a normal mouse had significant inflammation at the foot joint (left), while a mouse with increased amounts of TTP didn’t show inflammation. (Image: NIEHS)

This finding may eventually result in an oral medicine for the treatment of these inflammatory diseases in humans, the authors predicted.

In this study, researchers developed a mouse model in which the TTP gene expressed higher than normal amounts of the TTP protein. The researchers then tested the mice using experimental models of rheumatoid arthritis, psoriasis, and multiple sclerosis.

“Mice with more TTP in their bodies were resistant to the inflammation that accompanied these experimental models of disease,” said lead investigator Perry Blackshear, MD, DPhil, Senior Investigator at the National Institute of Environmental Health Sciences (NIEHS), in Research Triangle Park, NC.

“We also found evidence of how TTP is providing this protection”—presumably by dampening the excessive production of proinflammatory mediators, Dr. Blackshear added. TTP appears to target several messenger molecules that encode cytokines and chemokines. TTP binds to these molecules and destabilizes them, resulting in lower levels of proinflammatory mediators and, thus, decreased inflammation.

The researchers now hope to develop compounds that will produce a similar effect of raising TTP levels in the body. Dr. Blackshear expects that TTP-based treatments would be cost effective and easy to administer.

“Many current therapies for these inflammatory diseases are expensive and require the medicines be introduced into the body under the skin, in the muscle, or by intravenous injection,” said the study’s lead author Sonika Patial, DVM, PhD, a postdoctoral research fellow in Dr. Blackshear’s lab. “Our ideal treatments would be administered orally in pill or liquid form.” 

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