Navigation Links
Molecule that destroys bone also protects it, new research shows

An immune system component that is a primary cause of bone destruction and inflammation in autoimmune diseases such as rheumatoid arthritis actually protects bone in the oral cavity from infectious pathogens that play a major role in periodontal disease in humans, research at the University at Buffalo has shown.

The component, IL-17, was recognized only in the past 18 months to be a primary cause of bone destruction and inflammation in autoimmune diseases. Therapies that target IL-17 or its cellular receptor currently are being developed.

However, a UB molecular biologist has discovered that, in contrast to its action in rheumatoid arthritis(RA), IL-17 actually protects bone in the oral cavity from infectious pathogens such as Porphyromonas gingivalis, a bacterium that plays a major role in most periodontal disease in humans.

The research findings appear in the current (May) issue of the journal Blood.

Sarah L. Gaffen, Ph.D., associate professor of oral biology in the UB School of Dental Medicine and associate professor of microbiology and immunology in the UB School of Medicine and Biomedical Sciences, is senior author. Jeffrey J. Yu, a medical student and doctoral candidate who is a researcher working in Gaffen’s lab, is first author.

Gaffen and colleagues conducted the research in mice bred to have no receptors for IL-17. Other researchers had shown previously, using rats and mice as animal models, that blocking the receptor for IL-17 could be an effective therapy for RA and possibly for other autoimmune diseases such as multiple sclerosis, colitis, psoriasis and lupus.

The effects of an IL-17 deficiency in periodontal disease, however, were unknown, so Gaffen’s lab set out to investigate.

"I predicted these mice without the IL-17 receptor were going to be protected from periodontal bone loss, just like they’re protected from arthritic bone loss," Gaffen said. "In fact, we got the op posite result. The mice without IL-17 were much more susceptible to bone loss caused by periodontal disease, compared to normal mice.

"What’s the difference between an autoimmune disease like RA and periodontal disease" Periodontal disease is an infectious disease, and as with most infectious diseases, white blood cells of the innate immune system called neutrophils play a critical role in fighting infections. In fact, humans with neutrophil defects usually lose all their teeth by the time they are 20 due to severe periodontal disease.

"It turns out that IL-17 is really important in regulating neutrophils by causing other cells in the vicinity to recruit these infection fighters to the infection site," Gaffen said.

IL-17 is a cytokine, a protein hormone made by "T helper" cells of the immune system that stimulate immunity. Gaffen noted that until recently, immunologists believed there were only two major types of "T helper" cells -- TH1 and TH2 -- which were believed to be responsible for nearly all immune system activities.

"This paradigm underwent a sea change in 2005 with the discovery of a new type of T cell that produces IL-17, now called TH-17," she said. "We know now that almost all autoimmune diseases, at least in the mouse model, are caused by TH-17 cells. This new information has forced scientists to revise completely how they view their favorite disease. Everyone now has to rethink the causative mechanism."

Gaffen said IL-17 likely would be toxic if given systemically, so it may not be a therapeutic candidate to increase immunity. But inhibitors of IL-17 are considered important targets for drugs to treat autoimmune diseases such as RA and psoriasis.

On the down side, however, this new finding indicates that inhibiting IL-17 too much could put people taking such a drug at risk for opportunistic infections such as periodontal disease and tuberculosis, she noted.

"Developin g knowledge about the molecules that contribute to host defense versus pathology is very important for gaining a fundamental understanding of the immune system," Gaffen said, "but also because the consequences of therapies that target these cytokines need to be understood."
'"/>

Source:University at Buffalo


Related biology news :

1. DNA Molecules Used To Assemble Nanoparticles
2. Duke Chemists Isolating Individual Molecules Of Toxic Protein In Alzheimers, Parkinsons Disease
3. Molecule that usually protects infection-fighting cells may cause plaque deposits inside arteries
4. Successful Test Of Single Molecule Switch Opens The Door To Biomolecular Electronics
5. Touching Molecules With Your Bare Hands
6. Team Invents Device For Weighing Individual Molecules
7. Missing Receptor Molecule Causes Tumor Growth
8. Molecule by molecule, new assay shows real-time gene activity
9. Molecule does more than slice and dice RNA
10. Molecules in blood foretell development of preeclampsia
11. Green catalyst destroys pesticides and munitions toxins, finds Carnegie Mellon University

Post Your Comments:
*Name:
*Comment:
*Email:


(Date:2/2/2016)... 2, 2016   Parabon NanoLabs (Parabon) ... Army Research Office and the Defense Forensics and ... of the company,s Snapshot Kinship Inference ... more generally, defense-related DNA forensics.  Although Snapshot is ... appearance and ancestry from DNA evidence), it also ...
(Date:2/1/2016)... , Feb. 1, 2016  Today, the first ... (AHA) announced plans to develop a first of its ... power of IBM Watson. In the first application of ... IBM (NYSE: IBM ), and Welltok will create ... health assessments with cognitive analytics, delivered on Welltok,s health ...
(Date:1/27/2016)... Jan. 27, 2016  Rite Track, Inc. a leading ... West Chester, Ohio announced today the ... staff, based in Austin, Texas , ... to provide modifications, installations and technical support offerings for ... of PLUS, commented, "PLUS has provided world class service ...
Breaking Biology News(10 mins):
(Date:2/5/2016)... -- On Thursday, February 11, 2-1-1 San Diego ... and disaster services, and the Community Information Exchange ... coordination and service delivery for the community to better ... better connect service providers to the information they can ... has handled more than 2.5 million connections ...
(Date:2/4/2016)... - New FDA action date of July ... action date of July 22, 2016   --> ... 22, 2016   - Lifitegrast has the ... for the treatment of signs and symptoms of dry eye disease ... to be the only product approved in the U.S. in the past decade indicated for ...
(Date:2/4/2016)... 4, 2016 Beike Biotechnology, the ... attended a ceremony in late 2015 to mark their ... in 2016. --> --> ... for Personalized Cell Therapy" was hosted by the Shenzhen ... both subsidiaries of Beike Biotechnology Co., Ltd. ...
(Date:2/4/2016)... -- ContraVir Pharmaceuticals, Inc. (NASDAQ: CTRV ), a ... targeted antiviral therapies, announced today that it will present ... held February 8-9, 2016, at the Waldorf Astoria New ... Healthcare Conference, taking place in New York ... Sapirstein , Chief Executive Officer of ContraVir, will provide ...
Breaking Biology Technology: