Navigation Links
UC Davis researchers discover new drug target for inflammatory disease

(SACRAMENTO, Calif.) UC Davis researchers have defined a cellular process that promotes inflammation and, at the same time, found an important starting point for identifying and testing new drugs for diseases such as sepsis, rheumatoid arthritis, cardiovascular disease and some cancers.

The scientists discovered that a protein called sPLA2-IIA binds to two integrins labeled alpha-V-beta-3 and alpha-4-beta-1, causing them to rapidly multiply and boosting an immune system response already gone awry due to disease.

"We have known for a while that this protein is elevated with inflammation," said Yoshikazu Takada, UC Davis professor of dermatology and lead author of the study, which appears in the September 19 issue of The Journal of Biological Chemistry. "Our outcome shows with much more precision how the protein actually works to advance inflammation. The potential impact of the finding on our ability to block inflammation and stop the disease process in its tracks is enormous."

Protein sPLA2-IIA has been a major drug discovery target for years, but efforts to counteract the protein have yielded mixed results. Takada explains that this is due to the fact that its intercellular relationships in humans were not well-known. Scientists have previously identified receptors for the protein in mice cells. However, Takada and his team are the first to find that the protein binds to completely different receptors the two integrins in human cells.

Integrins are the "networkers" of the immune system, playing key roles in the attachment of cells to other cells. Integrins are also important to signal transduction, the process by which a cell transforms from one kind of signal or stimulus into another.

"We need to know the mechanisms of inflammation to be able to disrupt it," said Takada. "Now that we know more about how this protein interacts with these integrins, researchers can be much more successful in screening potential drugs that can block the binding process and hopefully the immune response it kicks into overdrive as well."

In the current study, Takada and team evaluated the possibility of integrin binding by sPLA2-IIA using a computer program that predicts how small molecules bind to receptors. They then performed laboratory experiments using human cells to confirm the resulting predictions.

The researchers conducted additional experiments using human leukemia and lymphoma cell lines, because they are known to express integrins, in order to measure changes in the inflammatory response due to sPLA2-IIA-integrin binding. They found an increase in the number of monocytes, which are important first-line defenders for the immune system responsible for attacking foreign substances in the body. At elevated levels, monocytes indicate an overresponsive immune system.

The involvement of integrins to the inflammatory process is of particular interest to study co-author Kit Lam, chief of hematology and oncology with UC Davis Cancer Center.

"These two and other integrins are found on cancer cells," Lam explained. "And inflammation certainly plays a role in the onset, progression and maintenance of certain cancers. This outcome could have a huge impact on our work in finding medications that halt or at least reduce the impact of inflammation on this disease."

Takada and his colleagues will next be working to screen for molecules that block the binding of sPLA2-IIA to integrins and show that this blockage is enough to shut down an unwanted inflammatory response.

"We cannot ignore integrins anymore," Takada said. "More basic research is needed to understand how integrin-binding results in pro-inflammatory signals. We have to continue to better understand the integrin signaling process if we are to find more potential drug targets for the treatment of inflammation."


Contact: Karen Finney
University of California - Davis - Health System

Related biology news :

1. UC Davis researchers define characteristics, treatment options for XXYY syndrome
2. UC Davis researcher leads climate-change discovery
3. UC Davis stem researchers demonstrate safety of gene therapy using adult stem cells
4. UC Davis researchers discover how HIV turns food-poisoning into lethal infection
5. UC Davis bird-flu expert calls for changes in early-warning system
6. Pittsburgh researchers identify source of multipotent stem cells with broad regenerative potential
7. U of M researchers identify gene linked to common ailment in labrador retrievers
8. Friendly bacteria protect against type 1 diabetes, Yale researchers find
9. Using novel tool, UD researchers dig through cell trash and find treasure
10. More than skin deep: Theres no such thing as a safe suntan, researchers warn
11. Flatworm helps researchers study stem cells and cancer
Post Your Comments:
(Date:10/29/2015)... Mich. , Oct. 29, 2015  Rubicon ... Genomics for U.S. distribution of its DNA library ... kit and Rubicon,s new ThruPLEX Plasma-seq kit. ThruPLEX ... enable the preparation of NGS libraries for liquid ... for diagnostic and prognostic applications in cancer and ...
(Date:10/27/2015)... 27, 2015 In the present market scenario, ... for various industry verticals such as banking, healthcare, defense, ... growing demand for secure & simplified access control and ... as hacking of bank accounts, misuse of users, , ... as PC,s, laptops, and smartphones are expected to provide ...
(Date:10/26/2015)... and LAS VEGAS , Oct. 26, ... , an innovator in modern authentication and a founding ... the launch of its latest version of the Nok ... organizations to use standards-based authentication that supports existing and ... Authentication Suite is ideal for organizations deploying customer-facing applications ...
Breaking Biology News(10 mins):
(Date:11/26/2015)... England , November 26, 2015 ... an innovative medical device company specializing in imaging technologies, announced ... the European Commission as part of the Horizon 2020 European ... to carry out a large-scale clinical trial in breast cancer. ...      (Logo: , --> ...
(Date:11/25/2015)... 2 nouvelles études permettent d , ... les souches bactériennes retrouvées dans la plaque dentaire ... . Ces recherches  ouvrent une nouvelle voie ... de l,un des problèmes de santé les plus ... --> 2 nouvelles études permettent d , ...
(Date:11/25/2015)... , Nov. 25, 2015  Neurocrine Biosciences, Inc. ... Gorman , President and CEO of Neurocrine Biosciences, will ... Conference in New York . ... visit the website approximately 5 minutes prior to the ... replay of the presentation will be available on the ...
(Date:11/25/2015)... Nov. 25, 2015 Orexigen® Therapeutics, Inc. (Nasdaq: ... in a fireside chat discussion at the Piper Jaffray ... . The discussion is scheduled for Wednesday, December ... .  A replay will be available for 14 ... , Julie NormartVP, Corporate Communications and Business Development ...
Breaking Biology Technology: