Regulatory effect of microRNA-135a on the Th1/Th2 imbalance in a murine model of allergic rhinitis

Luo, Yuejun; Deng, Yuxiao; Tao, Zezhang; Chen, Shiming; Xiao, Bokui; Ren, Jie; Chen, Zhe; Han, Jing; Kong, Yonggang; Xu, Yu; Deng, Mei

doi:10.3892/etm.2014.1855

Cited by 27 publications

(26 citation statements)

References 39 publications

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“…Inflammation in any tissue is known to involve the activation of eosinophils and degranulation of MCs, which in turn release a variety of pro-inflammatory mediators that can cause tissue damage [ 2 , 19 , 20 ] and trigger the expression and secretion of various biologically active chemicals [ 3 , 21 , 22 ]. For example, we previously found that stimulation with OVA increases the concentration of interleukin 4 (IL-4) [ 11 ], reflecting the symptoms of an allergic reaction similar to that observed in AR patients. In the present study, we confirmed that OVA increases the infiltration of eosinophils and MCs in the nasal mucosa in addition to increasing the total serum IgE concentration and Th2 cell differentiation in our AR mouse model.…”

Section: Discussionmentioning

confidence: 99%

“…Our decision to focus on the therapeutic potential of miR-135a stems from our previous work indicating that this miR-135a can specifically bind to GATA-3 and that overexpression of miR-135a in AR mice decreases the mRNA and protein expression of both GATA-3 and IL-4 [ 11 ]. Here, these data were confirmed and we further highlighted the ability of this miR-135a to decrease GATA-3 mRNA and protein expression and increase T-bet mRNA expression in the nasal mucosa.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, a previous computational investigation utilizing bioinformatics data indicated that simplex miRNA, including those in the miR-135 family, may have the ability to regulate the immune response by targeting GATA-3 and regulating the biased differentiation of T-helper 2 (Th2) cells observed during AR [ 10 ]. Moreover, we previously analyzed the 3′-UTR of murine GATA-3, focusing on the target sequences of the miR-135 family, using TargetScan and found a binding site specific for miR-135a, a microRNA that appears to be downregulated during AR [ 11 ]. In this prior work, we also overexpressed miR-135a in a mouse model of AR by administering a miR-135a mimic to induce native expression.…”

Section: Introductionmentioning

confidence: 99%

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Intranasal Administration of Lentiviral miR-135a Regulates Mast Cell and Allergen-Induced Inflammation by Targeting GATA-3

et al. 2015

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Mast cell (MC) degranulation is the foundation of the acute phase of allergic rhinitis (AR). Previously, downregulation of GATA binding protein 3 (GATA-3) was shown to suppress MC activation in an AR mouse model. Binding of microRNA-135a (miR-135a) to GATA-3 was also observed, and overexpression of this miRNA decreased GATA-3 mRNA and protein expression. However, the effects of miR-135a on MCs during AR are currently unknown. In the present study, we utilized a lentiviral (LV) vector to intranasally administer miR-135a to ovalbumin (OVA)-sensitized AR mice. Following miR-135a treatment, the total serum IgE concentration observed during AR was significantly reduced. In the nasal mucosa, the expression of T-box expressed in T cells (T-bet) was higher, whereas that of GATA-3 was lower in the AR mice following miRNA treatment. Notably, during AR, the ratio of type 1 T-helper cells (Th1) to type 2 (Th2) cells in the spleen is unbalanced, favoring Th2. However, administering miR-135a to the AR mice appeared to balance this ratio by increasing and decreasing the percentage of Th1 and Th2 cells, respectively. MiR-135a also appeared to strongly suppress the infiltration of eosinophils and MCs into the nasal mucosa, and it was specifically localized in the MCs, suggesting that its influence is modulated through regulation of GATA-3 in these cells. Additional work identifying the full therapeutic potential of miR-135a in the treatment of AR and diseases involving allergen-induced inflammation is warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Intranasal Administration of Lentiviral miR-135a Regulates Mast Cell and Allergen-Induced Inflammation by Targeting GATA-3

et al. 2015

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“…Several miRNAs have been demonstrated to influence the development, phenotypical stability and functions of Th2 cells. For example, miR-138 and miR-135a regulate the balance of Th1/Th2 in psoriasis by inhibiting runtrelated transcription factor 3 (RUNX3) expression [21,22].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-466a-3p attenuates allergic nasal inflammation in mice by targeting GATA3

Chen

Deng

et al. 2019

Clinical and Experimental Immunology

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Summary Allergic rhinitis is thought to be an allergic disease associated with immunoglobulin (Ig)E‐mediated immune response, characterized by increased T helper type 2 (Th2) cytokine production, elevated eosinophil levels in the nasal mucosa and induced nasal secretions. MicroRNA (miRNA) microarray data revealed that the expression level of miR‐466a‐3p was significantly decreased. Notably, GATA binding protein (GATA‐3) was identified as one of its target genes through miRNA target prediction web tools. The expression levels of miR‐466a‐3p were altered by mimics and lentivirus both in vivo and in vitro, similar to those of GATA‐3. Furthermore, the symptoms and histology of allergic rhinitis as well as the levels of serum IgE and interleukin (IL)‐4 were examined in different groups of mice. Interestingly, the results for lentiviral miR‐466a‐3p‐treated allergic rhinitis mice were relatively similar to normal mice, compared to allergic rhinitis mice without treatment. Also, miR‐466a‐3p negatively regulated GATA‐3 expression in allergic rhinitis mice, indicating the participant of Th2‐cell responses in allergic rhinitis. Taken together, our findings highlight a new perspective on the role of miR‐466a‐3p in allergic rhinitis. In addition, this study provides a theoretical framework and experimental reference for future research targeting microRNAs as therapeutic targets and diagnostic biomarkers of allergic rhinitis.

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“…AR is a common disease that serves as a risk factor for the development of other diseases, such as asthma (2). The symptoms of AR, including nasal congestion, rhinorrhea and sneezing, considerably affect the daily activities, quality of sleep and work productivity of patients (3).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑let‑7e regulates the progression and development of allergic rhinitis by targeting suppressor of cytokine signaling 4 and activating Janus kinase 1/signal transducer and activator of transcription 3 pathway

Zhang

Jiang

et al. 2018

Exp Ther Med

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Abstract. The present study aimed to explore the microRNA-let-7e (miR-let-7e) expression in allergic rhinitis (AR), and to investigate the underlying molecular mechanisms. miR-let-7e expression in the nasal mucosa of mice and patients with AR were detected. The expression levels of three inflammatory factors, including histamine, immunoglobulin E and tumor necrosis factor-α (TNF-α), in the blood of AR mice and in interleukin (IL)-13-stimulated nasal epithelial cells (NECs) were also measured. Furthermore, the target gene of miR-let-7e was predicted and validated using a luciferase reporter assay. The expression levels of Janus kinase 1 (JAK1) and signal transducer and activator of transcription 3 (STAT3) were detected. The results demonstrated that miR-let-7e was downregulated in patients and mice with AR compared with the controls. In addition, the expression levels of inflammatory factors were higher in the blood of mice with AR compared with the control group, while miR-let-7e overexpression inhibited these levels in AR mice and IL-13-stimulated NECs. Furthermore, suppressor of cytokine signaling 4 (SOCS4) was revealed as a potential target gene of miR-let-7e and was negatively regulated by miR-let-7e. Overexpression of SOCS4 abrogated the anti-inflammatory activity of miR-let-7e overexpression. Finally, miR-let-7e overexpression activated the JAK1/STAT3 signaling pathway. In conclusion, miR-let-7e may serve an important role in the progression and development of AR, while overexpression of miR-let-7e had an anti-inflammatory effect by targeting SOCS4, which may be achieved by activation of the JAK1/STAT3 signaling pathway.

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Regulatory effect of microRNA-135a on the Th1/Th2 imbalance in a murine model of allergic rhinitis

Cited by 27 publications

References 39 publications

Intranasal Administration of Lentiviral miR-135a Regulates Mast Cell and Allergen-Induced Inflammation by Targeting GATA-3

Intranasal Administration of Lentiviral miR-135a Regulates Mast Cell and Allergen-Induced Inflammation by Targeting GATA-3

MicroRNA-466a-3p attenuates allergic nasal inflammation in mice by targeting GATA3

MicroRNA‑let‑7e regulates the progression and development of allergic rhinitis by targeting suppressor of cytokine signaling 4 and activating Janus kinase 1/signal transducer and activator of transcription 3 pathway

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