Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Pro-inflammatory protein contributes to Crohn’s disease

04.02.2005


A pro-inflammatory protein activated by bacteria in the colon plays a key role in the development of experimental colitis in mice – a mouse-version of human Crohn’s disease – according to research by scientists at the University of California, San Diego (UCSD) School of Medicine.

The study, published in the February 4, 2005 issue of the journal Science, identified interleukin-1Beta (IL-1â) as a major cause of severe inflammation in the mouse model of Crohn’s disease, which is a painful, chronic and little-understood inflammatory bowel disease (IBD) in humans, affecting more than 500,000 Americans. These individuals are considered at high risk for colon cancer.

The identification of IL-1â offers a potential target for drug development, said the study’s senior author, Michael Karin, Ph.D., UCSD professor of pharmacology and an American Cancer Society Research Professor. Although there is currently an IL-1â inhibitor on the market for other, non-Crohn’s chronic inflammatory conditions such as rheumatoid arthritis, this drug is not a very potent IL-1â inhibitor. "Now that we’ve identified IL-1â as an important target for Crohn’s disease therapy, we hope that a better, more effective IL-1â inhibiting drug can be developed for testing its efficacy in these patients," Karin said.



Crohn’s disease is thought to involve an interaction between a genetic defect and environmental factors such as bacterial infections that trigger the disorder. Recently, scientists identified mutations in a gene called NOD2 as leading to 50 percent of Crohn’s cases in patients of Northern European descent, but they haven’t known just how NOD2 causes the severe inflammation associated with the disorder. An intracellular sensor for bacterial infection, normal NOD2 activates a protein called nuclear factor-kappaB (NF-kB), which is involved in the immune system’s rapid response to bacterial infection. It has been observed that many of the drugs currently used to help Crohn’s disease patients may also act as weak and nonspecific NF-kB inhibitors in addition to having many other activities. Given the new results in the study, drugs that are more potent and more specific inhibitors of NF-kB also need to be tested for their therapeutic effects on Crohn’s disease patients.

Karin, who has conducted extensive research over the years on NF-kB and related genes, developed mice with mutant NOD2, that is identical to what is found in many Crohn’s disease patients, and then introduced a bacterial infection into the walls of their colons. One-third of the mice bearing the mutation developed very severe colon inflammation and died, while the surviving animals had large lesions in their colons and lost a considerable amount of weight. His research team found that the mice bearing the NOD2 mutation also had markedly high levels of active NF-kB in the inflammatory cells (macrophages) that were present within their colons. Interestingly these mice also had high levels of mature IL-1â, a pro-inflammatory protein.

"The unique thing about IL-1â is that it is first made as a larger precursor that accumulates within the inflammatory cells but is usually very poorly secreted," Karin said, "only under certain circumstances, an enzyme called IL1 converting enzyme (ICE) is activated, the IL-1â precursors, whose synthesis is stimulated by NF-kB, are cleaved and the mature protein can be secreted. Therefore finding high levels of IL-1â secretion in the mutant mice suggested that in addition to activating the NF-kB, that mutant NOD2 also stimulated the processing of the IL-1â precursor into its mature form."

The Karin team then gave an IL-1â inhibitor to mice and it abolished the experimental colitis (Crohn’s Disease) in the mutant mice; none of the animals died and inflammation was considerably reduced.

Sue Pondrom | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Studies and Analyses:

nachricht Drone vs. truck deliveries: Which create less carbon pollution?
31.05.2017 | University of Washington

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

Im Focus: Optoelectronic Inline Measurement – Accurate to the Nanometer

Germany counts high-precision manufacturing processes among its advantages as a location. It’s not just the aerospace and automotive industries that require almost waste-free, high-precision manufacturing to provide an efficient way of testing the shape and orientation tolerances of products. Since current inline measurement technology not yet provides the required accuracy, the Fraunhofer Institute for Laser Technology ILT is collaborating with four renowned industry partners in the INSPIRE project to develop inline sensors with a new accuracy class. Funded by the German Federal Ministry of Education and Research (BMBF), the project is scheduled to run until the end of 2019.

New Manufacturing Technologies for New Products

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

A new technique isolates neuronal activity during memory consolidation

22.06.2017 | Life Sciences

Plant inspiration could lead to flexible electronics

22.06.2017 | Materials Sciences

A rhodium-based catalyst for making organosilicon using less precious metal

22.06.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>