Chronic obstructive pulmonary disease (COPD) leads to persistent inflammation of the airways and is typically managed with corticosteroids, a class of anti-inflammatory medication.
However, corticosteroids do not improve survival nor alter the progression of COPD and may reduce lung symptoms as little as 20 percent. A new study led by researchers at the Johns Hopkins Bloomberg School of Public Health, found why corticosteroids do not work well for COPD patients and how additional treatment with sulforaphane—an ingredient of broccoli and other vegetables—can improve the effectiveness of corticosteroids. The study was published online October 17, 2011, in advance of print in the Journal of Clinical Investigation.
COPD is a major public health problem for both the developed and the developing world, and is most often caused by cigarette smoking or exposure to pollutants from combustion. Characterized by chronic bronchitis and emphysema, COPD is the third leading cause of death in the U.S. and affects 24 million Americans and 210 million people worldwide.
Histone deacetylase 2 (HDAC2) is critical component in a chain of reactions that enable corticosteroids to reduce inflammation. However, HDAC2 is substantially reduced in the lung tissue of individuals with COPD. In the study, Johns Hopkins researchers found that S-nitrosylation causes HDAC2 dysfunction and leads to corticosteroid insensitivity in the alveolar macrophages of the lungs of individuals with COPD. S-nitrosylation of HDAC2 occurs from exposure to cigarette smoke, a primary cause of COPD.
“This study provides the mechanism of exaggerated inflammation observed in COPD patients during exacerbations, which has been a barrier to developing effective therapy,” said Rajesh Thimmulappa, PhD, co-author of the study and an assistant scientist in the Bloomberg School’s Department of Environmental Health Sciences.
Furthermore, the research team found that treatment with sulforaphane restored HDAC2 activity and corticosteroid sensitivity. Previous studies by the research team showed sulforaphane activates the Nrf2 pathway (nuclear factor erythroid 2–related factor 2) and it is being tested in clinical trial for patients with COPD.
“Restoring corticosteroid sensitivity in patients with COPD by targeting the Nrf2 pathway holds promise for effectively treating exacerbations,” said Shyam Biswal, PhD, senior author of the study and professor in the Bloomberg School’s Department of Environmental Health Sciences and Division of Pulmonary and Critical Care Medicine at the Johns Hopkins School of Medicine.
Authors of “Denitrosylation of HDAC2 by Targeting Nrf2 Restores Glucocorticosteriod Sensitivity in Macrophages from COPD Patient” are Deepti Malhotra, Rajesh Thimmulappa, Nicolas Mercado, Kazuhiro Ito, Ponvijay Kombairaju, Sarvesh Kumar, Jinfang Ma, David Feller-Kopman, Robert Wise, Peter Barnes and Shyam Biswal.
Funding for the research was provided by the National Institutes of Health, the National Heart, Lung and Blood Institute, the Flight Attendants Medical Research Institute, the National Cancer Institute, the National Institute on Environmental Health and the Grace Anne Dorney fund for tobacco-related disease research.
Biswal, Thimmulappa, and the Johns Hopkins University hold intellectual property on the development of Nrf2-based therapeutics in COPD, and they have equity in Cureveda LLC, which was co-founded by Biswal and Thimmulappa, and where they serve as scientific consultants. These potential individual and institutional conflicts of interest have been reviewed and managed by the Johns Hopkins Bloomberg School of Public Health. Under a licensing agreement between Brassica Protection Products and the Johns Hopkins University, the University is entitled to royalty received on sales of products/technology described in this article. The University owns Brassica Protection Products stock, which is subject to certain restrictions under University policy. The terms of this arrangement are being managed by the Johns Hopkins University in accordance with its conflict of interest policies. No other competing interest were declared.
Media contact, Johns Hopkins Bloomberg School of Public Health : Tim Parsons, director of Public Affairs, at 410-955-7619 or email@example.com
Tim Parsons | EurekAlert!
NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures
17.11.2017 | National Institute of Standards and Technology (NIST)
High speed video recording precisely measures blood cell velocity
15.11.2017 | ITMO University
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
17.11.2017 | Physics and Astronomy
17.11.2017 | Health and Medicine
17.11.2017 | Studies and Analyses