“We showed that an important component in red wine and also grapes called resveratrol can suppress inflammation,” said Dr. Jian-Dong Li, a senior author of the study, director of the Institute for Biomedical Sciences at Georgia State and a Georgia Research Alliance Eminent Scholar. “It has been shown that resveratrol can suppress inflammation, but how it regulates inflammation still remains largely unknown. We found that resveratrol suppresses a major bacterial pathogen causing otitis media and COPD by upregulating or increasing the production of a negative regulator called MyD88 short.”
Resveratrol belongs to a group of compounds called polyphenols that are thought to act like antioxidants and protect the body against damage. It has long been considered a therapeutic agent for various diseases, including inflammatory diseases. In the study, resveratrol was effective against inflammation caused by nontypeable Haemophilus influenzae (NTHi), a major respiratory pathogen.
An appropriate amount of inflammation in the body is beneficial for defense against bacterial infection, but uncontrolled inflammation leads to inflammatory diseases. Upper respiratory tract inflammatory diseases such as asthma and COPD affect more than half a billion people worldwide and are characterized by chronic inflammation that is aggravated by respiratory pathogens such as NTHi. Asthma results in 250,000 deaths annually and is the leading cause of hospitalizations in children younger than 15 in the United States. COPD is the third leading cause of death in the U.S., and the World Health Organization predicts it will be the fifth most significant contributor to worldwide disease by 2020. Otitis media is the most common bacterial infection and also the leading cause of conductive hearing loss in children.
Antibiotics are routinely used to treat NTHi infections, but the increasing numbers of antibiotic-resistant bacterial strains and the limited success of currently available pharmaceuticals used to manage the symptoms of these diseases present an urgent need for the development of non-antibiotic therapeutics.
This study found for the first time that resveratrol decreases NTHi-induced expression of pro-inflammatory mediators in airway epithelial cells and in the lungs of mice by enhancing MyD88 short, a negative regulator of inflammatory signaling pathways. MyD88 short is considered a “brake pedal protein” because it can tightly control inflammation induced by this respiratory pathogen. It could be a critical target with significant therapeutic potential for suppressing inflammation associated with chronic airway disease.
The researchers also found that resveratrol has anti-inflammatory effects after NTHi infection, which demonstrates its therapeutic potential.
“The findings help us to shed light on developing new therapeutic strategies by targeting or pharmacologically upregulating MyD88 short production,” Li said. “We could use resveratrol to suppress inflammation or develop resveratrol derivatives that could be pharmacological agents to suppress inflammation using the same strategy.”
Co-authors of the study include first author Carla S. Andrews, Shingo Matsuyama and Byung-Cheol Lee of the Center for Inflammation, Immunity and Infection in the Institute for Biomedical Sciences at Georgia State.
The study was funded by the National Institutes of Health’s National Institute on Deafness and Other Communication Disorders and National Institute of General Medical Sciences.