Oenophiles have advocated the pleasures and benefits of drinking red wine for centuries. However, much of the basis for the medicinal value of the burgundy spirit has been anecdotal at best. Yet, over the past several decades, reliable, hypothesis-driven research has uncovered a few components of red wine with some unique properties. Resveratrol, a natural polyphenolic compound found in red wine grapes and other dark-skinned berries, has led the way in potential health benefits.
Now, investigators from Georgia State University have found that resveratrol can help control inflammation induced by a bacterial pathogen that is linked to upper respiratory tract inflammatory diseases, such as asthma, chronic obstructive pulmonary diseases (COPD), and middle ear infection (otitis media). The researchers were able to identify a novel mechanism that the compound uses to alleviate inflammation in airway disease—suggesting that it could offer health benefits and be used to develop new, effective anti-inflammatory therapeutic agents.
“We showed that an important component in red wine and also grapes called resveratrol can suppress inflammation,” explained senior study investigators Jian-Dong Li, M.D., Ph.D., director of the Institute for Biomedical Sciences at Georgia State University. “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 [myeloid differentiation factor 88] short.”
Resveratrol has long been thought to act as an antioxidant, protecting 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.
The authors wrote that they showed “for the first time that resveratrol decreases expression of pro-inflammatory mediators in airway epithelial cells and in the lung of mice by enhancing NTHi-induced MyD88 short, a negative regulator of inflammation, via inhibition of ERK1/2 activation. Furthermore, resveratrol inhibits NTHi-induced ERK1/2 phosphorylation by increasing MKP-1 expression via a cAMP-PKA-dependent signaling pathway.”
The findings from this study were published recently in Scientific Reports in an article entitled “Resveratrol Suppresses NTHi-Induced Inflammation Via Up-Regulation of the Negative Regulator MyD88 Short.”
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.
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 nonantibiotic therapeutics.
The Georgia State team found that resveratrol decreases NTHi-induced expression of proinflammatory 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.
“Together these data reveal a novel mechanism by which resveratrol alleviates NTHi-induced inflammation in airway disease by up-regulating the negative regulator of inflammation MyD88s,” the authors penned.
“The findings help us to shed light on developing new therapeutic strategies by targeting or pharmacologically upregulating MyD88 short production,” Dr. Li added. “We could use resveratrol to suppress inflammation or develop resveratrol derivatives that could be pharmacological agents to suppress inflammation using the same strategy.”