Key pathway to stop dangerous, out-of-control inflammation discovered

A potential new strategy to developing new drugs to control inflammation without serious side effects has been found by Georgia State University researchers and international colleagues.

Jian-Dong Li, director of Georgia State's Center for Inflammation, Immunity and Infection, and his team discovered that blocking a certain pathway involved in the of inflammation will suppress it.

Inhibiting a molecule called phosphodiesterase 4B, or PDE4B, suppresses inflammation by affecting a key gene called CLYD, a gene that serves as a brake on inflammation.

The research was published in the journal Nature Communications.

Li explained the process of overactive inflammation using a "police" analogy.

When a pathogen – such as bacteria or viruses—infects a patient, he said, it triggers an "alarm" to which the "police" of immune system respond. In turn, it triggers neutrophil attractant called cytokines to respond, leading to inflammation that serves to help rid the body of the pathogen. But if inflammation isn't stopped, can result.

The pathways during the response are termed "positive," like a gas pedal on a car, and "negative," like a brake, with the process in the positive pathway going down the line from the pathogen to inflammation, and negative going the other direction. PDE4B is involved in controlling the negative pathway.

Many researchers have been focusing on developing anti- by stopping the positive pathway, but the discovery by Li and his colleagues gives scientists a new route to stop inflammation using safer or even existing drugs proven to be non-toxic as they have found that accelerating the negative will reduce inflammation.

"This is the key negative regulator that we have been searching after for years, " Li said.

There is a need for better drugs to control inflammation, because current treatments come with serious side effects, Li said. Steroids are commonly used, but cannot be used over the long-term. Steroids suppress the immune system.

More information: The article is "Inhibition of PDE4B suppresses inflammation by increasing expression of the deubiquitinase CLYD," in Nature Communications, available at hx.doi.org/10.1038/ncomms6274

Related Stories

Penn researchers discover how key protein stops inflammation

Aug 08, 2007

Researchers at the University of Pennsylvania School of Medicine recently identified how a regulatory protein called Bcl-3 helps to control the body’s inflammation response to infection by interfering a critical biochemical ...

Recommended for you

Ontario has one of the highest rates of IBD in the world

Aug 28, 2014

One in every 200 Ontarians has been diagnosed with inflammatory bowel disease (IBD), with the number of people living with the disease increasing by 64 per cent between 1999 and 2008, according to a study by researchers at ...

New drug promises relief for inflammatory pain

Aug 27, 2014

Pain from inflammation sidelines thousands of Americans each year. Many face a tough choice: deal with the pain, take a potentially addictive opioid or use a nonsteroidal anti-inflammatory drug that may increase risk for ...

Overweight causes hazardous inflammations

Aug 25, 2014

Researchers have found a possible molecular explanation for why overweight is harmful. This new knowledge may provide new drugs for heart attack, stroke, cancer and chronic intestinal inflammation.

Asthma outcomes worse in older women

Aug 21, 2014

(HealthDay)—Older women face increased challenges in managing their asthma, according to a review published in the August issue of the Annals of Allergy, Asthma & Immunology.

User comments