Bronchial asthma, a chronic inflammatory disease of the airways that is reversible in certain cases, usually presents with cough, difficulty of breathing, and wheezing. Although most people can successfully control asthma using inhaled corticosteroids, approximately 10% of patients are resistant to treatment. Recent evidence has suggested a link between the excessive intake of fatty acids and exacerbation of asthma, but the details of the relationship had remained elusive.
In a study recently published in the Journal of Allergy and Clinical Immunology, a research group from the University of Tsukuba shed light on this knowledge gap. The group focused on the function of an enzyme called ELOVL6, which is responsible for the biosynthesis of long-chain fatty acids in humans. Dysfunction of ELOVL6 has been linked to various immune-related conditions, and thus, the group hypothesized a link between ELOVL6 and asthma.
“Improper function of ELOVL6 has been linked to diseases, such as atopic dermatitis, which is similar to asthma; both are related to immune response-mediated inflammation” explains senior author Yuko Morishima. “To investigate the role of ELOVL6 in asthma, we created an asthma mouse model that was lacking the ELOVL6 enzyme and investigated its fatty acid profile and allergen-response of the mouse airways.” The group also assessed the levels of ELOVL6 in the airways of severely asthmatic patients.
The data confirmed that the expression of ELOVL6 is reduced in patients with severe asthma i.e., patients whose asthma was not controlled despite intense treatment. Interestingly, there was no significant difference in the patients’ BMI when compared to non-asthmatic controls, which concurs with the groups data in the mouse model that showed that a deletion of ELOVL6 affected the fatty acid composition in mouse lungs but did not contribute to weight gain. Furthermore, the mice lacking ELOVL6 had enhanced airway inflammation, as well as enhanced goblet cell hyperplasia and airway responsiveness in response to allergens.
The study revealed that deletion of ELOVL6 increased the amounts of a class of lipids called ceramides in mice airways and also resulted in increased levels of a ceramide metabolite called S1P. “S1P is known to be potentially related to allergic inflammation, thus we wondered what effect inhibiting its synthesis would have on our ELOVL6-deficient mouse model,” says Morishima. “Fascinatingly, we found that drug-induced inhibition of ceramide and S1P synthesis reduced not only airway inflammation in our model but also reduced the migration of immune cells out of lymph nodes and their cytokine production.”
These results partially uncovered the mechanism of treatment-resistant asthma, showing that the composition of lipids is pivotal in the inflammatory response. Importantly, the study provided a proof-of-concept of a novel treatment method for recalcitrant asthma by modulating the lipid composition, setting the groundwork for future studies.
more recommended stories
Personalized brain modeling technique may lead to breakthroughs in clinical epilepsy trial
Researchers of the Human Brain Project.
Investigative reporter, who covered murder-suicides, explains how journalists are vulnerable to trauma
It never really dawned on me.
Got gastroenteritis? Here’s why eating bananas helps but drinking flat lemonade might not
Doctors are reportedly concerned about a spike in.
Immunotherapy combined with targeted therapy for colorectal cancer yields promising outcomes for patients
A new study that used insights.
How total abortion ban puts maternal health at risk
Pregnant patients in El Salvador, who,.
Scientists find that microRNA affects inflammation in lupus disease.
A group of researchers from the.
Researchers unveil new collection of human brain atlases that chart postnatal development
Human brain atlases can be used.
New hope for patients with hereditary metabolic disorder
Methylmalonic aciduria (MMA) is a metabolic.
Keys to making immunotherapy work against pancreatic cancer found in tumor microenvironment
A new study that analyzed the.
Study shows correlation between poor sleep and suicide risk in college-aged adults
A study led by researchers in.