Abstract
BackgroundThis study was designed to investigate the mechanism and effects of miRNA-221-5p on the T-helper 17 (Th17)/T-regulatory (Treg) ratio in asthma.MethodsBALB/c mice were intranasally challenged with 100 µg OVA on 14 and 21 day. Mice were rechallenged with 2.5% OVA-PBS on 22 and 28 day. Mice were sacrificed using on day 30 under 35 mg/kg pentobarbital sodium. PBMCs were induced vitro model of asthma using 500 ng of lipopolysaccharides (LPS) for 4 h.ResultsThe expression of miRNA-221-5p was reduced in in vivo model, compared sham group. The vitro model of asthma treated with miRNA-221-5p mimic resulted in the reduction of IL-6, IL-17, IL-21 and IL-22 levels, and induction of IL-10, IL-35 and TGF-β levels. In addition, down-regulation of miRNA-221-5p induced the protein expression of suppressor of cytokine signaling 1 (SOCS1) and receptor-related orphan receptor-gamma-t (RORγt) and suppressed that of FOXP3 in in vitro model of asthma. Over-expression of miRNA-221-5p induced the protein expression of FOXP3, and suppressed that of SOCS1 and RORγt in in vitro model of asthma. The inhibition of SOCS1 or RORγt attenuated the effects of anti-miRNA-221-5p on Th17/Treg ratio in asthma.ConclusionmiRNA-221-5p may play critical roles in driving the differentiation of Th17/Treg ratio via RORγt/Foxp3 by Targeting SOCS1, reduced the function of Th17 cells by directly inhibiting RORγt/SOCS1 and promoted the function of Treg cells via Foxp3/ SOCS1 in asthma.
Highlights
This study was designed to investigate the mechanism and effects of miRNA-221-5p on the T-helper 17 (Th17)/T-regulatory (Treg) ratio in asthma
The expression of miRNA‐221‐5p in asthma To explore the roles of miRNA-221-5p in Treg and Th17 cells ratio of asthma, the expression level of miRNA-221-5p was first measured in model of asthma
Th17 cells were increased while Treg cells were reduced in model of asthma, in comparison with sham group (Fig. 1A–D)
Summary
This study was designed to investigate the mechanism and effects of miRNA-221-5p on the T-helper 17 (Th17)/T-regulatory (Treg) ratio in asthma. Bronchial asthma (asthma) has become a frequently-occurring and common disease in clinical practice due to changes in the environment and climate [1]. The monocyte proportion of peripheral blood helper T cells (Th17) in children with respiratory syncytial virus (RSV) bronchiolitis was higher than that in children with pneumonia and healthy children. The percentage of regulatory T cells (Treg cells) in CD4+ T cells in children with RSV bronchiolitis was lower than that of children with pneumonia and healthy children. These results suggest that Th17/Treg imbalance is related to the development of bronchiolitis [2, 4]. Th17 cells can mediate the occurrence of airway inflammation in neutrophilic asthma [5]
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