Navigation Links
Study identifies novel role for a protein that could lead to new treatments for rheumatoid arthritis
Date:5/22/2011

A new study by rheumatologists at Hospital for Special Surgery in New York has shown that a powerful pro-inflammatory protein, tumor necrosis factor (TNF), can also suppress aspects of inflammation. The researchers say the identification of the mechanism of how this occurs could potentially lead to new treatments for diseases such as rheumatoid arthritis. The study was published May 22 online in advance of publication in the journal Nature Immunology.

"Prior to this study, TNF has long been known as a potent pro-inflammatory cytokine, but if you look carefully through the literature, there are hints that it also has some suppressive functions, but nothing was known about the mechanisms," said Lionel Ivashkiv, M.D., associate chief scientific officer and physician in the Arthritis and Tissue Degeneration Program at Hospital for Special Surgery who led the study. "This is really the first mechanism showing how TNF can turn inflammation down."

Because many proteins have homeostatic functions, both driving and suppressing certain actions so a cell can maintain internal equilibrium, researchers thought TNF might not be an exception. "Most strong activators in the immune system trigger a feedback response to restrain the amount of inflammation," Dr. Ivashkiv said.

To find out, researchers designed experiments stimulating macrophages with lipopolysaccharide (LPS), a prototypical inflammatory factor that stimulates receptors important in inflammation. In test tube studies, the researchers treated human monocytes and macrophages, cells that have a key role in inflammatory diseases, with TNF and then challenged these cells with LPS. They found that the TNF suppressed the inflammatory response of the macrophages and monocytes. They then gave mice low doses of TNF followed by high doses of LPS and found that the mice were protected from the effects of high dose LPS, which is usually lethal. They discovered that the mechanism by which TNF suppressed the inflammatory response involved a protein known as GSK3 (glycogen synthase kinase 3-alpha) and a gene known as TNFAIP3 that encodes the A20 protein. Experiments with a drug that can inhibit GSK3 as well as experiments with RNA interference of A20, which can block A20 gene function, helped identify the roles of this protein and gene.

The researchers say the findings could be used to develop potential therapies for diseases, such as rheumatoid arthritis. "We think it is relevant to rheumatoid arthritis, not only because the cells we are studying (the macrophages) are exactly the same cells that migrate into joints and make the inflammatory cytokines involved in rheumatoid arthritis, but because A20 is involved. TNFAIP3 is one of the best linked genes to rheumatoid arthritis," Dr. Ivashkiv said. "There are polymorphisms in the A20 gene that have been linked to RA pathogenesis."

The researchers hypothesize that patients who make less A20 are more susceptible to inflammation and thus rheumatoid arthritis. One approach to treating RA could be to increase A20 levels in patients who naturally make less A20 by manipulating GSK-3, since this study showed that GSK-3 influences A20. "The study sort of opens a line of investigation to understanding how A20 levels can be manipulated in patients with various diseases," Dr. Ivashkiv said.

The findings could be applied to other diseases besides arthritis. In conditions such as rheumatoid arthritis, you may want to boost A20, but in other settings such as cancer, where the macrophages are suppressed, you may want to inhibit A20 expression.

"What the study shows that is new is that TNF has suppressive functions in addition to its well-known activating functions," Dr. Ivashkiv said. "Before this study, people thought it might suppress adaptive immunity, but surprisingly we found that it actually suppresses a cell of the innate immune system, the macrophage, which is the same cell that makes it and, by doing that, it regulates its own production."


'/>"/>

Contact: Phyllis Fisher
phyllis.fisher@gmail.com
212-606-1197
Hospital for Special Surgery
Source:Eurekalert

Related medicine news :

1. Despite Treatment, Employees with Depression Generate Higher Absentee Costs, According to Thomson Reuters Study
2. American Council on Exercise (ACE) Study Reveals Kettlebells Provide Powerful Workout in Short Amount of Time
3. TV drama can be more persuasive than news program, study finds
4. Study carried out into biological risks of eating reptiles
5. Neuroimaging study may pave way for effective Alzheimers treatments
6. Study finds racial gaps continue in heart disease awareness
7. Luth Researchs IndicatorEDG(TM) Study Finds Americans Hopes of Achieving Their Dreams Are Fading
8. First blinded study of venous insufficiency prevalence in MS shows promising results
9. Soothing infants with food focus of childhood obesity study
10. People with anxiety disorder less able to regulate response to negative emotions, study shows
11. American Heart Association Rapid Access Journal Report: Study Finds Racial Gaps Continue in Heart Disease Awareness, Low Knowledge of Heart Attack Warning Signs Among Women
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... (PRWEB) , ... October 13, 2017 , ... Apple ... care services, staged a mock evacuation of the facility as part of a disaster ... Fire Department, Echo Hose EMS and Shelton City Emergency Manager, as well as the ...
(Date:10/13/2017)... , ... October 13, 2017 , ... Global Healthcare Management’s ... Alexandria Park in Milford, NJ. This free event, sponsored by Global Healthcare Management’s ... The fun run is geared towards children of all ages; it is a ...
(Date:10/13/2017)... ... October 13, 2017 , ... “The Journey: From the ... danger possible to save lost souls in the Philippines. “The Journey: From the Mountains ... a dedicated teacher of the Bible. She has taught all ages and currently teaches ...
(Date:10/12/2017)... ... October 12, 2017 , ... Planet Fitness, one of the largest and ... plans to open a flagship location in Covington, LA at 401 N. U.S. Highway ... store next to Office Depot in the Holiday Square shopping center. Its location allows ...
(Date:10/12/2017)... ... 2017 , ... Asante, a nationally recognized health system in ... existing home health joint venture through an agreement, effective October 1, 2017, to ... home health company with Asante, delivering clinically integrated care, for the past eight ...
Breaking Medicine News(10 mins):
(Date:10/10/2017)... -- NDS received FDA 510(k) clearance in May 2017 for its highly ... designed for endoscopy environments. An innovative secondary monitor solution, ZeroWire ... support the improvement of patient outcomes, procedural efficiency, and the lowering ... ... ...
(Date:10/4/2017)... 4, 2017  South Korean-based healthcare product Development Company ... "cprCUBE" on Kickstarter. The device will educate the user ... with better efficiency compared to the dated and pricey ... on efficacy of the compression for a more informed ... goal to raise $5,000. ...
(Date:10/2/2017)... 2017  Eli Lilly and Company (NYSE: ... third quarter of 2017 on Tuesday, October 24, 2017. ... day with the investment community and media to further ... call will begin at 9 a.m. Eastern time. Investors, ... webcast of the conference call through a link that ...
Breaking Medicine Technology: