Mechanism Explains How Resveratrol Reduces Upper Respiratory Inflammation

The red wine component resveratrol reduces inflammation in the upper respiratory tract by enhancing the activity of the protein MyD88 short, a negative regulator of inflammatory signaling pathways.

Resveratrol is found primarily in the skin and seeds of grapes. The amount found in grape skins varies with the grape cultivar, its geographic origin, and exposure to fungal infection. The amount of fermentation time a wine spends in contact with grape skins is an important determinant of its resveratrol content. Epidemiological and experimental reports have linked mild-to-moderate wine and/or grape consumption to a lowered risk of cardiovascular, cerebrovascular, and peripheral vascular diseases.

The MyD88 (Myeloid differentiation primary response gene 88) gene encodes a cytosolic adapter protein that plays a central role in the innate and adaptive immune response. This protein functions as an essential signal transducer in the interleukin-1 and Toll-like receptor signaling pathways. These pathways regulate that activation of numerous pro-inflammatory genes. Patients with defects in this gene have an increased susceptibility to bacterial infections.

Upper respiratory tract inflammatory diseases such as asthma and chronic obstructive pulmonary diseases (COPD) affect more than 500 million people globally and are characterized by chronic inflammation that is often exacerbated by respiratory pathogens such as nontypeable Haemophilus influenzae (NTHi). 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 novel anti-inflammatory therapeutic agents.

Investigators at Georgia State University (Atlanta, USA) reported in the September 28, 2016, online edition of the journal Scientific Reports that resveratrol decreased expression of pro-inflammatory mediators in airway epithelial cells and in the lungs of mice by enhancing NTHi-induced MyD88 short, a negative regulator of inflammation, via inhibition of ERK (Extracellular signal–regulated kinases) 1/2 activation. Furthermore, resveratrol inhibited NTHi-induced ERK1/2 phosphorylation by increasing MKP-1 (MAP kinase phosphatase) expression via a cAMP-PKA (Protein kinase A)-dependent signaling pathway. In addition, they showed that resveratrol had anti-inflammatory effects following NTHi infection, thereby demonstrating its therapeutic potential.

“We showed that an important component in red wine and also grapes called resveratrol can suppress inflammation,” said senior author Dr. Jian-Dong Li, director of the institute for biomedical sciences at Georgia State. “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. The findings help us to shed light on developing new therapeutic strategies by targeting or pharmacologically upregulating MyD88 short production. We could use resveratrol to suppress inflammation or develop resveratrol derivatives that could be pharmacological agents to suppress inflammation using the same strategy.”

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Georgia State University