COPD-associated inflammation halted in model experiment

May 4, 2018, Helmholtz Association of German Research Centres
Microscopic image of an iBALT. Credit: Helmholtz Zentrum München

Chronic obstructive pulmonary disease (COPD), is believed to be the third most common cause of death worldwide. However, because the underlying mechanism is still largely unknown, today's treatments can only slow progression of the disease. Scientists at Helmholtz Zentrum München have now reported a previously unknown pathogenic mechanism, which they have already been able to prevent in the laboratory. Their findings are reported in EMBO Molecular Medicine.

Cigarette smoking and general environmental pollution pose the greatest risks for COPD and lead to an inflammatory reaction in the airways and lung tissue. As a result, sufferers develop chronic cough, sputum production and shortness of breath. In the long term, is destroyed, which makes breathing more difficult.

In a recent paper, a team led by Dr. Ali Önder Yildirim shed new light on the inflammatory process. "We focused on tertiary lymphoid organs in the bronchi," explains Yildirim, one of the acting directors of the Institute of Lung Biology at Helmholtz Zentrum München, a member of the German Center for Lung Research (DZL). Specifically, the researchers studied what is known as inducible bronchus-associated lymphoid tissue, or iBALT for short. "It is believed that the development of iBALT plays a key role in the deterioration of COPD, but until now, it was unclear exactly how iBALT forms," says Yildirim.

Therefore, the specialists looked for known processes in other lymphoid tissues. In this context, their attention was drawn to the metabolism of oxysterols. Oxysterols are derivatives of cholesterol that play a role in a wide range of biological processes, including the positioning of in lymphoid tissue.

"We wanted to find out whether that is also the case around the lungs and specifically in cigarette-smoke-induced COPD," Yildirim says. In fact, the researchers found elevated levels of enzymes involved in oxysterol metabolism together with immune cells that migrate into the tissue both in the and in the lungs of COPD patients. Further experiments also showed that iBALT formation is inhibited if the metabolic enzymes are absent. Their absence also prevented the migration of immune cells and damage to the lungs despite exposure to cigarette smoke.

The scientists then attempted to recreate this effect pharmacologically by blocking the oxysterol pathway with an inhibitor, which they found prevented the immune cell migration following cigarette smoke irritation and therefore iBALT formation in the experimental model. "Our future goal is to transfer the results from the model to humans with a view to intervening in the development of COPD," Ali Önder Yildirim says. "There is still a lot of work to do, however we are very much looking forward to it."

Explore further: Age-related inflammatory processes facilitate development of COPD

More information: Jie Jia et al, Cholesterol metabolism promotes B‐cell positioning during immune pathogenesis of chronic obstructive pulmonary disease, EMBO Molecular Medicine (2018). DOI: 10.15252/emmm.201708349

Related Stories

Age-related inflammatory processes facilitate development of COPD

June 17, 2015
At present, there is a lack of effective treatments that target the causes of chronic obstructive pulmonary disease (COPD). Scientists of the Comprehensive Pneumology Center (CPC) at Helmholtz Zentrum München are therefore ...

Cigarette smoke curbs lung's self-healing

March 2, 2017
Smoke from cigarettes blocks self-healing processes in the lungs and consequently can lead to chronic obstructive pulmonary disease (COPD). Researchers at the Helmholtz Zentrum München, partner in the German Center for Lung ...

Oxysterols guide gut immune cells and are involved in inflammatory bowel disease

January 16, 2018
Researchers at Karolinska Institutet in Sweden report that cholesterol metabolites cause specific immune cells in the large intestine to move, which lies behind the formation of the immune system's important lymphoid tissue ...

Protective effect of CD9 and CD81 in COPD and accelerated aging

April 17, 2018
Chronic obstructive pulmonary disease (COPD) is an inflammatory disease that causes obstructed airflow, and it is expected to be the third leading cause of death globally by 2030. At present, only symptomatic therapies for ...

Study: Almost 100 million adults have COPD in China

April 10, 2018
Chronic obstructive pulmonary disease (COPD) is widespread in China with 8.6 percent of the country's adult population - almost 100 million people -suffering from the chronic lung disease, according to a new Tulane University ...

COPD – what causes the lungs to lose their ability to heal?

December 16, 2016
In chronic obstructive pulmonary disease (COPD), the patients' lungs lose their ability to repair damages on their own. Scientists at the Helmholtz Zentrum München, partner in the German Center for Lung Research (DZL) now ...

Recommended for you

A new approach to developing a vaccine against vivax malaria

September 21, 2018
A novel study reports an innovative approach for developing a vaccine against Plasmodium vivax, the most prevalent human malaria parasite outside sub-Saharan Africa. The study led by Hernando A. del Portillo and Carmen Fernandez-Becerra, ...

Pre-clinical success for a universal flu vaccine offers hope for third generation approach

September 21, 2018
Researchers from the University of Oxford's Department of Zoology have demonstrated pre-clinical success for a universal flu vaccine in a new paper published in Nature Communications.

Researchers define possible molecular pathway for neurodegeneration in prion diseases

September 21, 2018
A new study has shed light on the mechanisms underlying the progression of prion diseases and identified a potential target for treatment.

Fighting a deadly parasite: Scientists devise a method to store Cryptosporidium, aiding vaccine research efforts

September 21, 2018
In May, just before one of the hottest summers on record, the U.S. Centers for Disease Control and Prevention issued a warning about diseases lurking in recreational water facilities like swimming pools and water playgrounds. ...

Scientists make significant discovery in the fight against drug-resistant tuberculosis

September 20, 2018
A team of scientists have identified a naturally occurring antibiotic that may help in the fight against drug-resistant Tuberculosis.

Anti-cancer drugs may hold key to overcoming antimalarial drug resistance

September 20, 2018
Scientists have found a way to boost the efficacy of the world's most powerful antimalarial drug with the help of chemotherapy medicines, according to new research published in the journal Nature Communications.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.