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New therapeutic target identified for rheumatoid arthritis
Date:11/5/2008

we knew that the Notch pathway was important in development and that the Toll-like receptor pathways were important in acute inflammation, and now we know that those two things are linked in acute inflammation and cytokine production," said Dr. Ivashkiv.

When molecules dock on the Toll-like receptors of macrophages, proteins including interleukin-6, which has been implicated in rheumatoid arthritis, are produced. In another experiment, investigators showed that the production of interleukin-6 was decreased if a protein called RBP-J was not present. Investigators also found that interfering with the production of RBP-J decreased the activation of certain Notch target genes.

"The Toll-like receptors regulate the Notch pathway, but the Notch pathways also regulates the Toll-like receptors, and it all seems to be through this RBP-J protein," said Dr. Ivashkiv. He says that other studies have shown that drugs called gamma secretase inhibitors have been shown to interfere with the Notch pathway and thus could be used to treat rheumatoid arthritis by decreasing the amount of interleukin-6.


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Contact: Phyllis Fisher
fisherp@hss.edu
212-606-1197
Hospital for Special Surgery
Source:Eurekalert

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