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:10/13/2017)... ... October 13, 2017 , ... As health professionals work ... as “patient engagement.” The patient is doing more than filling out a survey; in ... “There is an increasing emphasis in health care and research on the importance of ...
(Date:10/13/2017)... ... October 13, 2017 , ... The American Board of Family ... next President and Chief Executive Officer, succeeding Dr. James C. Puffer upon his retirement. ... 1, 2018 until Dr. Puffer’s retirement at the end of 2018. Upon assuming the ...
(Date:10/13/2017)... ... October 13, 2017 , ... PurhealthRX , a ... utilizing Purzorb™ technology. Applying the Purzorb™process to full spectrum CBD oil will revolutionize the ... a CBD form that can be easily incorporated into liquid products, while reducing costs ...
(Date:10/13/2017)... ... 13, 2017 , ... Lori R. Somekh, founder of the Law Office ... of elder law and special needs planning attorneys. “Membership in ElderCounsel helps our office ... forum to network with elder law attorneys nationwide,” said Somekh. , ElderCounsel ...
(Date:10/13/2017)... , ... October 13, 2017 , ... Many families have ... many long-term care insurance companies have a waiver for care if the client has ... period, when the family pays for care, is often waived, so the benefits from ...
Breaking Medicine News(10 mins):
(Date:9/28/2017)... 28, 2017 Cohen Veterans Bioscience and Early ... of wearable and home sensors for real-time monitoring of ... Foundation, a nonprofit organization focused on disruptive health solutions ... affordable analytical system to record and integrate behavioral, cognitive, ... ...
(Date:9/25/2017)... 2017  EpiVax, Inc., a leader in the ... today announced the launch of EpiVax Oncology Inc., ... therapeutic cancer vaccines. EpiVax has provided $500,000 in ... enabling technologies to the new precision immunotherapy venture. ... Oncology as Chief Executive Officer. Gad brings over ...
(Date:9/19/2017)... a venture-backed medical device company developing a non-invasive, robotically assisted, platform therapy that uses pulsed ...   ... Jim Bertolina, ... Tom Tefft ... medical device executive Josh Stopek , PhD, who has led R&D and business development ...
Breaking Medicine Technology: