Navigation Links
Jefferson scientists uncover key pathway, potential drug targets in autoinflammatory disease
Date:11/12/2007

(PHILADELPHIA) Molecular biologists at Jeffersons Kimmel Cancer Center in Philadelphia have detailed the cascade of cellular events behind some potentially dangerous autoinflammatory diseases. In doing so, they not only have gained a greater understanding of the disease process, but have also identified new potential drug targets for diseases ranging from arthritis to cancer.

Reporting in the journal Molecular Cell, Emad Alnemri, Ph.D., professor of Biochemistry and Molecular Biology at Jefferson Medical College of Thomas Jefferson University, and his co-workers describe how two proteins called PSTPIP1 and pyrin interact to cause autoinflammatory diseases, inherited diseases characterized by seemingly unprovoked and recurrent attacks of fever and inflammation. Such diseases have been found largely to be caused by defects in proteins that regulate inflammation.

According to Dr. Alnemri, defects in pyrin, for example, have been linked to familial Mediterranean fever, a sometimes fatal disease found in the Mediterranean, Middle East and Europe. Defects in PSTPIP1 have been linked to a rare, autoinflammatory disease called PAPA syndrome. The two proteins apparently worked together in the same inflammatory pathway, but no one understood how these proteins could lead to disease.

Dr. Alnemri and his co-workers figured out how. They found that mutant forms of PSTPIP1 found in patients with PAPA syndrome can turn on pyrin, which eventually leads to activating a potent inflammation-causing protein, IL-1 beta. Once activated, IL-1 beta can cause inflammation, fever and the production of other related substances.

Dr. Alnemri explains, Because mutant PSTPIP1 proteins interact with pyrin much more strongly than normal PSTPIP1, they cause uncontrolled or exaggerated activation of pyrin and consequently more secretion of IL-1 beta in these patients.

These proteins now become potential therapeutic targets, Dr. Alnemri says. For example, there is a synthetic analog of the IL-1 receptor antagonist called Anakinra that has been successfully used in clinical trials to treat autoinflammatory diseases, including PAPA syndrome and familial Mediterranean fever, in addition to other chronic inflammatory diseases such as rheumatoid arthritis.

He explains that IL-1 beta binds to a receptor on the cell membrane that induces the inflammatory phenotype. Anakinra mimics IL-1 beta and binds to the same receptor, preventing IL-1 beta from binding and consequently blocking its effects on cells. Detailing these mechanisms is not only important for autoinflammatory disease, but for most inflammatory disease in general.

Chronic inflammation has been linked to the development of cancer, Dr. Alnemri points out. IL-1 beta appears to play a major role in tumor growth. Elevated concentrations of IL-1 beta have been found in aggressive forms of colon, breast and lung cancers. Its not clear how IL-1 beta promotes cancer growth, but the data suggest that in addition to its ability to stimulate production of inflammatory factors, it also stimulates cells to produce angiogenic factors to enhance angiogenesis, or the development of tumor-growth promoting blood vessels.

Dr. Alnemri adds that IL-1 beta antagonists are being tested against cancer in animal models with notable success, so you might actually be able to treat some forms of cancer by targeting proteins upstream in the inflammatory pathways, such as caspase-1, pyrin or PSTPIP1 to stop the generation of IL-1 beta.

The team plans next to investigate the role of inflammation in cancer. The researchers would like to study the potential involvement of the inflammatory pathways that they have identified, and whether anti-inflammatory agents that could affect such pathways can also affect cancer.


'/>"/>

Contact: Steve Benowitz
steven.benowitz@jefferson.edu
215-955-5291
Thomas Jefferson University
Source:Eurekalert

Related medicine news :

1. Jefferson specialists studying innovative surgery for effectively treating sleep apnea
2. Jefferson immunology researchers halt lethal rabies infection in brain
3. Jefferson radiation oncologists use real-time system to plant seeds against cancer
4. Jefferson researchers find personalized interventions key to improving colon cancer screening rates
5. Jefferson researchers uncover new evidence of prolactins possible role in breast cancer
6. MicroRNAs may be key to HIVs ability to hide, evade drugs, Jefferson scientists find
7. Jefferson scientists find protein may be key in developing deadly form of pancreatic cancer
8. Jefferson oncologists show focused radiation is effective as surgery against nerve tumor
9. Jefferson researchers find stem cells in degenerating spinal discs, potential for repair
10. Jefferson researchers show chemotherapy and radiation together extend lung cancer patients lives
11. Jefferson neuroscientists show anti-inflammation molecule helps fight MS-like disease
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/28/2017)... ... 28, 2017 , ... Starting in May, patients at The Bay Clinic ... (HRV) diagnostic test. , Nerve-Express, originally designed for the Navy in the 1980s, measures ... a patient’s autonomic nervous system (ANS). The ANS controls all the critical unconscious ...
(Date:5/28/2017)... ... May 28, 2017 , ... ... is proud to announce that Jorge Fernandez-Silva, M.D., has joined its new Melbourne ... a specialty that concentrates on minimally invasive techniques to treat and manage many ...
(Date:5/28/2017)... ... May 28, 2017 , ... Viewers likely know Rob Lowe from such 80s ... noted for his work on NBC’s The West Wing and Parks and Recreation. But ... series “Informed,” which puts the spotlight on important modern-day issues that face today’s society. ...
(Date:5/27/2017)... ... ... dentist? You should go twice per year for checkups, but if you want to keep ... some dental tips to help out: , 1. Brushing Teeth - Brush your teeth twice ... locker at school for a quick brushing after lunch. Use a small brush head with ...
(Date:5/27/2017)... ... May 27, 2017 , ... From May 21-23, hearing healthcare ... three-day event was held at the Marriott Syracuse Downtown Hotel in Syracuse, New York. ... and network of independent hearing healthcare providers to help them stay ahead in the ...
Breaking Medicine News(10 mins):
(Date:5/26/2017)... , May 25, 2017  In response to ... , Direct Relief is working with Pfizer to ... available at no cost to community health centers, free ... providers nationwide. "Pfizer has a long-standing ... medicines and ensuring patient safety through educational activities," said ...
(Date:5/22/2017)... , May 22, 2017  Lilac Corp, ... Gene-Eden-VIR/Novirin, announces the launch of a new ... the results of a clinical study that showed ... treatment with Gene-Eden-VIR/Novirin in individuals suffering from HPV ... note that there are no other treatments that ...
(Date:5/18/2017)... N.J. , May 17, 2017  Bayer announced ... oncology portfolio will be presented at the 53 rd ... Oncology (ASCO), taking place June 2-6 in ... presented at ASCO span prostate, colorectal, liver and thyroid ... analysis from the Phase II CHRONOS-1 trial of copanlisib ...
Breaking Medicine Technology: