Researchers discover new signaling pathway linked to inflammatory disease

Dec 14, 2010

Scientists at the University of California, San Diego School of Medicine have described for the first time a key inhibitory role for the IL-1 signaling pathway in the human innate immune system, providing novel insights into human inflammatory bowel disease (IBD) and potential new treatments.

The research, led by Jose M. Gonzalez-Navajas, PhD, and Eyal Raz, MD, a professor of medicine at UC San Diego, is published as a Brief Definitive Report in the December issue of The .

The researchers report that signaling by the interleukin 1 receptor (IL-1R) controls expression of a protein called DUBA (deubquitinase A), which in turn affects production of anti-inflammatory cytokines reacting to certain bacterial stimuli. Cytokines are molecules that help trigger an immune system response to infections and cancer. Some induce inflammation, some suppress it.

The IL-1R is essential to producing key anti-inflammatory cytokines like IL-10 and type 1 interferon, but , infection and some drugs can disrupt the signaling process, resulting in reduced or increased cytokine production that upsets delicate balances and leads to disease. Laboratory mice deficient in IL-1R type signaling were shown to produce fewer anti-inflammatory cytokines and were more susceptible to a condition similar to human . Human IBD encompasses a group of disorders affecting the colon and . The major types are Crohn's disease and ulcerative colitis.

The authors said the research also revealed the deleterious effects of some anti-inflammatory drugs. IL-1 is a pro-inflammatory cytokine implicated in certain conditions like rheumatoid arthritis and gout, the latter a painful inflammation of the toes and feet. The authors propose that several drugs currently used to treat these conditions by blocking IL-1 activity could be harmful to patients suffering from IBD, which generally involves an overwhelming immune response against normal, non-pathogenic gut bacteria.

"Our findings indicate that the use of such drugs can be harmful and therefore should be avoided in such patients," said Raz.

Explore further: Growing a blood vessel in a week

add to favorites email to friend print save as pdf

Related Stories

2 immune-system proteins linked to colitis-associated cancer

Feb 02, 2009

Recent research from the laboratory of Michael Karin, PhD, at the University of California, San Diego School of Medicine - the first researcher to demonstrate a molecular link between inflammation and cancer - has identified ...

Genetic variant predicts poor response to bypass surgery

Jan 29, 2009

A variant of the gene for the inflammatory modulator interleukin (IL)-18 has been found to be associated with a prolonged ICU stay after cardiopulmonary bypass (CPB) surgery. Research published in BioMed Central's open access ...

Recommended for you

Growing a blood vessel in a week

Oct 24, 2014

The technology for creating new tissues from stem cells has taken a giant leap forward. Three tablespoons of blood are all that is needed to grow a brand new blood vessel in just seven days. This is shown ...

Testing time for stem cells

Oct 24, 2014

DefiniGEN is one of the first commercial opportunities to arise from Cambridge's expertise in stem cell research. Here, we look at some of the fundamental research that enables it to supply liver and pancreatic ...

Team finds key signaling pathway in cause of preeclampsia

Oct 23, 2014

A team of researchers led by a Wayne State University School of Medicine associate professor of obstetrics and gynecology has published findings that provide novel insight into the cause of preeclampsia, the leading cause ...

Rapid test to diagnose severe sepsis

Oct 23, 2014

A new test, developed by University of British Columbia researchers, could help physicians predict within an hour if a patient will develop severe sepsis so they can begin treatment immediately.

User comments : 0