Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein involved in cystic fibrosis also plays role in emphysema, chronic lung disease

30.12.2010
A team of Johns Hopkins Children's Center researchers has discovered that a protein involved in cystic fibrosis (CF) also regulates inflammation and cell death in emphysema and may be responsible for other chronic lung diseases.

The findings, published online in the December issue of The Journal of Immunology, pave the way toward new treatments to prevent lung damage caused by infections or cigarette smoke in emphysema.

The protein, called CFTR (cystic fibrosis transmembrane conductance regulator), is already well known for its role in transporting chloride in and out of cells. In CF, the protein's chloride-carrying ability is absent due to genetic mutations, resulting in the buildup of thick sticky mucus in the lungs, which causes lung infections and breathing problems.

But the new Hopkins study indicates that CFTR is involved in immune regulation and immune response on a far wider scale. The research — conducted in mice and using lung tissue from people with and without emphysema — shows that those with lung damage from emphysema had less CFTR on the cell surface and that changes in the level of CFTR corresponded directly to disease severity. Decreases in CFTR also corresponded to increased buildup in the lung cells of a fatty molecule called ceramide, a well-known trigger of inflammation and cell death. Thus, the researchers say, by regulating ceramide's inflammation-causing activity, CFTR appears to be a watchdog for inflammation and cell death.

"Our findings suggest that CFTR is a multi-tasker protein that is not only involved in chloride transport but also in regulating cell death and inflammation by keeping in check the rampant and dangerous accumulation of ceramide," said principal investigator Neeraj Vij, Ph.D., a pulmonary researcher at Hopkins Children's and assistant professor at the Johns Hopkins University School of Medicine.

To elucidate the role played by cigarette smoking — the leading cause of emphysema — the researchers analyzed CFTR and ceramide levels in lung tissue obtained from non-smokers and from light and heavy former or current smokers. To further explore the link between cigarette smoke, CFTR and ceramide, the researchers compared lung tissue from mice with "virgin" lungs never exposed to smoke to tissue from the lungs of mice exposed to cigarette smoke for five hours a day over five days. The lungs of smoke-exposed mice had decreased CFTR expression and increased ceramide levels, thus confirming the role of cigarette smoke in lung damage. The heavier the smoking, the greater the lung damage, the lower the CFTR expression and the higher the ceramide accumulation, the researchers noted, clearly linking CFTR and ceramide levels to smoking history and disease severity.

Beyond clarifying the link between CFTR, ceramide and lung damage, the Hopkins team explained just how CFTR causes ceramide to trigger lung-damaging inflammation. Analyzing lung cells from people and mice lacking CFTR in their cell membrane under a microscope and with a technique called flow cytometry that captures changes in inflammatory and protein markers, the scientists noticed increased clustering of ceramide molecules on sections of the cell membrane called lipid rafts, known to be hot spots where inflammatory signaling proteins congregate. This clustering, the researchers said, leads to increased inflammatory signaling, greater inflammation and cell damage, but cells with normal CFTR had no such clustering. Apparently, the researchers say, when functioning properly CFTR keeps a lid on the signaling activity of inflammatory receptors by preventing them from clustering, thus warding off inflammation and lung damage.

"We anticipate that membrane CFTR and ceramide may turn out to be useful predictors of susceptibility to lung damage from smoking and infections and may be tailored for drug therapy to alter disease course," Vij said.

To further test their hypothesis, the researchers used two types of ceramide inhibitors to treat mice with lung damage caused by a bacterial infection. One of the inhibitors, FB1, successfully decreased ceramide buildup in mice with intact CFTR but failed to stop ceramide accumulation in mice with absent CFTR, as is the case in CF. However, the other type of inhibitor, AMT, curbed ceramide activity in the mice with the absent CFTR, while failing to do so in those with decreased CFTR.

"Each inhibitor appeared to be effective based on the levels of membrane CFTR and ceramide, suggesting two different therapies tailored to treat lung damage stemming from two distinct lung disorders — emphysema and CF," said co-investigator Manish Bodas, Ph.D., a post-doctoral fellow in Vij's lab at Hopkins Children's.

The research was funded by the National Institutes of Health and the Flight Attendant Medical Research Institute. Co-investigators in the study included Taehong Min and Steven Mazur, both of Hopkins.

Related:

Neeraj Vij Profile http://www.hopkinschildrens.org/Neeraj-Vij-PhD.aspx

Neeraj Vij Lab http://web.jhu.edu/vij

PubMed Publication http://www.ncbi.nlm.nih.gov/pubmed/21135173

Founded in 1912 as the children's hospital of the Johns Hopkins Medical Institutions, the Johns Hopkins Children's Center offers one of the most comprehensive pediatric medical programs in the country, with more than 92,000 patient visits and nearly 9,000 admissions each year. Hopkins Children's is consistently ranked among the top children's hospitals in the nation. Hopkins Children's is Maryland's largest children's hospital and the only state-designated Trauma Service and Burn Unit for pediatric patients. It has recognized Centers of Excellence in dozens of pediatric subspecialties, including allergy, cardiology, cystic fibrosis, gastroenterology, nephrology, neurology, neurosurgery, oncology, pulmonary, and transplant. For more information, visit www.hopkinschildrens.org

Ekaterina Pesheva | EurekAlert!
Further information:
http://www.jhmi.edu

More articles from Life Sciences:

nachricht The big clean up after stress
25.05.2018 | Julius-Maximilians-Universität Würzburg

nachricht Complementing conventional antibiotics
24.05.2018 | Goethe-Universität Frankfurt am Main

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

When corals eat plastics

24.05.2018 | Ecology, The Environment and Conservation

Surgery involving ultrasound energy found to treat high blood pressure

24.05.2018 | Medical Engineering

First chip-scale broadband optical system that can sense molecules in the mid-IR

24.05.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>