Researchers Discover Protein To Control Inflammation – Could Lead To Treatments For Rheumatoid Arthritis And Diabetes

Researchers Discover Protein To Control Inflammation – Could Lead To Treatments For Rheumatoid Arthritis And Diabetes

Youhai Chen

(Best Syndication) Pennsylvania researchers have discovered a key regulator protein called Bcl-3 which helps the body control the inflammation response to infections. The protein does this by interfering with a critical biochemical process called ubiquitination. Previous studies found that Bcl-3 plays a role in immunity, but this is the first research to suggest it regulates inflammation by blocking ubiquitination.

Diabetes, sepsis, and rheumatoid arthritis could be treated in the future by gene therapy. “The novelty of our study is the discovery that Bcl-3 acting on gene expression has a profound effect on inflammation,” according to Ruaidhri Carmody, PhD, Senior Research Investigator in the Department of Pathology and Laboratory Medicine and first author of the Science paper.

Youhai Chen, PhD, Associate Professor of Pathology and Laboratory Medicine, working with Carmody, discovered Bcl-3-deficient mouse cells respond to infection. Using mouse cells Chen found that Bcl-3 interacts with the p50 protein which inhibits gene transcription by binding to DNA.

“By mimicking Bcl-3 activity, we may be able to create an artificial way to block the inflammatory response,” the researchers report. “p50 turns off the DNA region coding for inflammation, halting the response to infection,” explains Chen. Without Bcl-3 the p50 cannot stop the inflammation response, but instead will become degraded very fast, through ubiquintination.

“Our study identifies another layer of information that controls the inflammatory response,” says Chen. “Bcl-3 appears to take in information from the body and, in response to infection, interferes with p50 degradation to decrease inflammatory response.”

“Inflammation is natural,” says Chen. “If we didn’t respond to infectious agents, bacteria would kill us. However, the inflammatory response must be controlled or we could also die. Bcl-3 helps regulate inflammation.”

“By using what we now know about Bcl-3 regulatory function, we hope to create new ways to control inflammation for therapeutic purposes with selective anti-inflammatory agents,” says Carmody.

Many of the drugs used to suppress inflammation can cause many undesirable side effects in patients with inflammatory diseases.

“Current drug treatments target inflammation signaling pathways. When you inhibit entire pathways, you can produce negative side effects,” said Carmody. “Since Bcl-3 acts on specific genes, we should be able to target a subset of dangerous regulatory genes without disrupting other important immune responses.” Such drugs could benefit patients with chronic inflammation and transplant recipients as well as those suffering with inflammatory diseases.

In the future, the scientists aim to determine the components of the cell responsible for flagging p50 for destruction and instructing Bcl-3 to perform its vital function.

The research is published in this issue of Science.

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By Jeffrey Workman
Best Syndication News Health Writer



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