Animals; Anti-Inflammatory Agents, Non-Steroidal (pharmacology, therapeutic use); Asthma (drug therapy, immunology, pathology); Bronchoalveolar Lavage Fluid (chemistry, immunology); Cytokines (immunology, metabolism); Disease Models, Animal; Down-Regulation (drug effects, immunology); Female; Forkhead Transcription Factors (genetics, immunology); Humans; Inflammation (drug therapy, immunology, pathology); Lung (drug effects, immunology, pathology); Mice; Mice, Inbred BALB C; MicroRNAs (metabolism); Ovalbumin (administration & dosage, immunology); Resveratrol (pharmacology, therapeutic use); T-Lymphocytes, Regulatory (drug effects, immunology, metabolism); Treatment Outcome
Asthma is a chronic inflammatory disease of airways mediated by T-helper 2 (Th2) cells involving complex signaling pathways. Although resveratrol has previously been shown to attenuate allergic asthma, the role of miRNA in this process has not been studied. We investigated the effect of resveratrol on ovalbumin-induced experimental allergic asthma in mice. To that end, BALB/c mice were immunized with ovalbumin (OVA) intraperitoneally followed by oral gavage of vehicle (OVA-veh) or resveratrol (100 mg/kg body) (OVA-res). On day 7, the experimental groups received intranasal challenge of OVA followed by 7 days of additional oral gavage of vehicle or resveratrol. At day 15, all mice were euthanized and bronchioalveolar fluid (BALF), serum and lung infiltrating cells were collected and analyzed. The data showed that resveratrol significantly reduced IL-5, IL-13, and TGF-β in the serum and BALF in mice with OVA-induced asthma. Also, we saw a decrease in CD3+CD4+, CD3+CD8+, and CD4+IL-4+ cells with increase in CD4+CD25+FOXP3+ cells in pulmonary inflammatory cell infiltrate in OVA-res group when compared to OVA-veh. miRNA expression arrays using lung infiltrating cells showed that resveratrol caused significant alterations in miRNA expression, specifically downregulating the expression of miR-34a. Additionally, miR-34a was found to target , as evidenced by enhanced expression of in the lung tissue. Also, transfection studies showed that miR-34a inhibitor upregulated expression while miR-34a-mimic downregulated expression. The current study suggests that resveratrol attenuates allergic asthma by downregulating miR-34a that induces increased expression of , a master regulator of Treg development and functions.
Digital Object Identifier (DOI)
Published in Frontiers in Immunology, Volume 9, 2018.
© 2018 Alharris, Alghetaa, Seth, Chatterjee, Singh, Nagarkatti and Nagarkatti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Alharris, E., Alghetaa, H., Seth, R., Chatterjee, S., Singh, N., Nagarkatti, M., & Nagarkatti, P. (2018). Resveratrol Attenuates Allergic Asthma and Associated Inflammation in the Lungs Through Regulation of miRNA-34a That Targets FoxP3 in Mice. Frontiers In Immunology, 9. https://doi.org/10.3389/fimmu.2018.02992