A new 'on' signal for inflammation

(Medical Xpress)—Inflammation is an important response in the body - it helps you to kill off invaders such bacteria that could cause a harmful infection. But if it's chronic or uncontrolled, inflammation can also cause trouble in conditions including rheumatoid arthritis, inflammatory bowel disease and a potentially fatal immune reaction to infection called sepsis.

A new study involving UCD researchers has discovered a signal that appears to trigger inflammation when the threat of a looms, and the experiments have also been able to block the signal in lab models, pointing to possible new approaches to treating .

The study, which was published in Nature and led by Trinity College Dublin, found that in the presence of a potential bacterial threat, called change how they burn energy. This switch in burning eventually leads to the build-up of a molecule called succinate in the cells, and this in turn triggers a chain of biochemical events that encourage inflammation.

One link in that chain is a molecule called hypoxia-induced factor 1a (HIF-1a). HIF-1a is best known for its role in helping you adapt to conditions of low oxygen, such as when you climb a high mountain and the ambient dip, explains Conway Fellow, Professor Cormac Taylor from UCD School of Medicine & Medical Science.

"When you go to high altitude, this factor gets expressed in cells and that helps to increase the number of red blood cells in your blood, so you can adapt to the lower oxygen," he explains.

But that's not the only place that HIF-1a has a job to do. "At time of stress including inflammation you also experience an activation of this HIF pathway," says Prof Taylor. "And previous work in our lab has looked at this in models of ."

In the new study, which was led by Prof Luke O'Neill at Trinity, Prof Taylor and Research Fellow Dr Eoin Cummins from UCD helped to work out that in macrophages sensing a bacterial threat, the build-up of succinate seems to 'tell' HIF-1a to switch on an inflammatory gene.

"In this case, HIF drives a gene called interleukin-1, which is a potent pro-inflammatory gene," explains Prof Taylor. "And that will contribute to the inflammatory process."

The new study makes an important link between energy burning processes in the immune system and an 'on' signal for inflammation, according to Prof Taylor. The research also showed that a drug usually used for epilepsy was able to tone down this succinate/HIf-1a pathway in a lab model of sepsis, and this could point to new approaches to intervening when inflammation is running out of control, he adds.

"It's a big emerging area, the links between metabolism, or energy burning, and inflammation in disease," says Prof Taylor. "And in the future we could be targeting these metabolic pathways for beneficial purposes in inflammation."

Related Stories

Illuminating cross talk between signalling factors

Nov 22, 2011

(Medical Xpress) -- Hypoxia and inflammation are environmental features occuring simultaneously in a variety of diseases such as growing tumours and critically inflamed tissues. UCD scientists investigating the relative contributions ...

Researchers link stress and pancreatic cancer in new paper

Feb 15, 2013

Pancreatic cancer is a deadly disease with increased incidences in the recent years. According to NDSU researchers, epidemiological data show chronic stress in a negative social and psychological state such as depression ...

Recommended for you

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

13 hours ago

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