Mechanism of miR-181a-5p in Regulatory T/T-Helper 17 Immune Imbalance and Asthma Development in Mice with Allergic Rhinitis

2021 ◽  
pp. 1-14
Author(s):  
Ruoyun He ◽  
Yujuan Chen ◽  
Xiaoer Chen ◽  
Binfan Yuan
Keyword(s):  
Allergic Rhinitis ◽  
Immunoglobulin E ◽  
High Mobility ◽  
Lavage Fluid ◽  
Chromosomal Protein ◽  
T Helper ◽  
T Helper 17 ◽  
Immune Disorder ◽  
Ifn Γ ◽  
Immune Imbalance

<b><i>Introduction:</i></b> Allergic rhinitis (AR) is an immune disorder and also a risk factor of asthma. microRNAs (miRNAs) are implicated in autoimmune diseases, including RA. This study investigated effect of miR-181a-5p on regulatory T (Treg)/ T-helper (Th) 17 immune imbalance in AR. <b><i>Methods:</i></b> A murine model of AR was established and treated with lentivirus modified miR-181a-5p. The allergic symptoms of mice were examined. The contents of Th17-related cytokines (interferon [IFN]-γ and interleukin [IL]-6), Treg-related cytokine (IL-10), and Treg-specific nuclear transcription factor (Foxp3) in nasal mucosa and lung tissues were determined. The proportion of Treg and Th17 cells was analyzed by flow cytometry. The level of ovalbumin-specific immunoglobulin E in the serum, and the contents of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid and IFN-γ, IL-6, and IL-10 in nasal lavage fluid were measured. The targeting relationship between miR-181a-5p and high mobility group box chromosomal protein 1 (HMGB1) was verified. HMGB1 and receptor for advanced glycation end products (RAGE) expression in RA were determined, and the interaction between HMGB1 and RAGE was detected. <b><i>Results:</i></b> miR-181a-5p expression was reduced in AR mice. miR-181a-5p overexpression attenuated allergic behaviors, alleviated Treg/Th17 imbalance, and delayed asthma development. HMGB1 and RAGE were elevated in AR mice. miR-181a-5p targeted HMGB1, and HMGB1 bound to RAGE, while miR-181a-5p overexpression reduced the binding between them. Activating HMGB1/RAGE reversed the protective effect of miR-181a-5p overexpression on AR and induced the development of asthma. <b><i>Conclusion:</i></b> miR-181a-5p overexpression reduced the binding of HMGB1 and RAGE by inhibiting HMGB1, thus alleviating Treg/Th17 immune imbalance and blocking AR from developing into asthma.

scholarly journals Apigenin Attenuates Allergic Responses of Ovalbumin-Induced Allergic Rhinitis Through Modulation of Th1/Th2 Responses in Experimental Mice

Dose-Response ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 155932582090479 ◽  
Author(s):  
Feng Chen ◽  
Dongyun He ◽  
Bailing Yan
Keyword(s):  
Allergic Rhinitis ◽  
Messenger Rna ◽  
Immunoglobulin E ◽  
Elevated Serum ◽  
Lavage Fluid ◽  
Specific Ige ◽  
Cytokine Signaling ◽  
Nuclear Factor ◽  
Th2 Response ◽  
Ifn Γ

Background: Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated immune-inflammatory response mainly affecting nasal mucosa. Apigenin, a flavonoid, has been documented to possess promising anti-allergic potential. Aim: To determine the potential mechanism of action of apigenin against ovalbumin (OVA)-induced AR by assessing various behavioral, biochemical, molecular, and ultrastructural modifications. Materials and Methods: Allergic rhinitis was induced in BALB/c mice (18-22 grams) by sensitizing it with OVA (5%, 500 μL, intraperitoneal [IP] on each consecutive day, for 13 days) followed by intranasal challenge with OVA (5%, 5 μL per nostril on day 21). Animals were treated with either vehicle (distilled water, 10 mg/kg, IP) or apigenin (5, 10, and 20 mg/kg, IP). Results: Intranasal challenge of OVA resulted in significant induction ( P < .05) of AR reflected by an increase in nasal symptoms (sneezing, rubbing, and discharge), which were ameliorated significantly ( P < .05) by apigenin (10 and 20 mg/kg) treatment. It also significantly inhibited ( P < .05) OVA-induced elevated serum histamine, OVA-specific IgE, total IgE, and IgG1 and β-hexosaminidase levels. Ovalbumin-induced increased levels of interleukin (IL)-4, IL-5, IL-13, and interferon (IFN)-γ in nasal lavage fluid were significantly decreased ( P < .05) by apigenin. Ovalbumin-induced alterations in splenic GATA binding protein 3 (ie, erythroid transcription factor) (GATA3), T-box protein expressed in T cells (T-bet), signal transducer and activator of transcription-6 (STAT6), suppressor of cytokine signaling 1 (SOCS1), nuclear factor-kappa B (NF-κB), and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha messenger RNA, as well as protein expressions were significantly inhibited ( P < .05) by apigenin. It also significantly ameliorated ( P < .05) nasal and spleen histopathologic and ultrastructure aberration induced by OVA. Conclusion: Apigenin regulates Th1/Th2 balance via suppression in expressions of Th2 response (IgE, histamine, ILs, GATA3, STAT6, SOCS1, and NF-κB) and activation of Th1 response (IFN-γ and T-bet) to exert its anti-allergic potential in a murine model of OVA-induced AR.

Bifidobacterium longum IM55 and Lactobacillus plantarum IM76 alleviate allergic rhinitis in mice by restoring Th2/Treg imbalance and gut microbiota disturbance

2019 ◽  
Vol 10 (1) ◽  
pp. 55-67 ◽  
Author(s):  
W.-G. Kim ◽  
G.-D. Kang ◽  
H.I. Kim ◽  
M.J. Han ◽  
D.-H. Kim
Keyword(s):  
T Cells ◽  
Allergic Rhinitis ◽  
Regulatory T Cells ◽  
Gut Microbiota ◽  
Lactobacillus Plantarum ◽  
Immunoglobulin E ◽  
Bifidobacterium Longum ◽  
Lavage Fluid ◽  
Th2 Cells

This study aimed to examine whether probiotics, which suppressed the differentiation of splenic T cells into type 2 helper T (Th2) cells and induced into regulatory T cells in vitro, alleviate allergic rhinitis (AR) and gut microbiota disturbance. We isolated Bifidobacterium longum IM55 and Lactobacillus plantarum IM76 from human faecal microbiota and kimchi, respectively, and examined their effects on ovalbumin (OVA)-induced AR and gut microbiota disturbance in mice. Treatment with IM55, IM76, or their probiotic mixture (PM) significantly reduced OVA-induced allergic nasal symptoms and blood immunoglobulin E (IgE) levels in mice. These also reduced OVA-induced interleukin (IL)-4 and IL-5 levels in nasal tissues and bronchoalveolar lavage fluid (BALF) but increased OVA-suppressed IL-10 levels. Treatment with IM55, IM76, or PM reduced OVA-induced increase in the populations of mast cells, eosinophils, and Th2 cells and increased OVA-suppressed population of regulatory T cells in the BALF. Treatment with IM55, IM76, or PM also inhibited OVA-induced expression of IL-5 in lung and colon tissues and restored OVA-disturbed composition of gut microbiota Proteobacteria, Bacteroidetes, and Actinobacteria. These results suggest that IM55 and IM67 can alleviate AR by restoring Th2/Treg imbalance and gut microbiota disturbance.

scholarly journals Honeysuckle extract relieves ovalbumin-induced allergic rhinitis by inhibiting AR-induced inflammation and autoimmunity

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Bin Lin ◽  
Bijuan Cai ◽  
Huige Wang
Keyword(s):  
Allergic Rhinitis ◽  
Nasal Mucosa ◽  
Inflammatory Reaction ◽  
Lavage Fluid ◽  
Nasal Lavage ◽  
Autoimmune Response ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protein Levels ◽  
Nasal Lavage Fluid ◽  
Ifn Γ

Abstract Honeysuckle has antiviral, antioxidative and anti-inflammatory properties. Allergic rhinitis (AR) is induced by immunoglobulin E (IgE)-mediated inflammatory reaction. Our study investigates whether honeysuckle extract (HE) has therapeutic effect on AR. An AR model of mice was established by ovalbumin (OVA). Hematoxylin–Eosin staining was used to assess nasal mucosa damage. Enzyme-linked immunosorbent assay (ELISA) was performed to determine serum histamine, IgE and interleukin (IL)-2, IL-4, IL-17 and interferon-γ (IFN-γ) from nasal lavage fluid. Western blot was carried out to analyze the protein level from nasal mucosa tissue. We found that HE not only decreased nasal rubbing and sneezing in AR mice, but also reduced AR-induced damage to nasal mucosa. Moreover, HE lowered the levels of serum IgE and histamine and inhibited IL-4 and IL-17 levels from AR mice but raised IL-2 and IFN-γ levels in AR-induced nasal lavage fluid. Our results also showed that HE elevated the protein levels of forkhead box P3 (Foxp3) and T-box transcription factor (T-bet) in AR-induced nasal mucosa tissue, whereas it inhibited signal transducer and activator of transcription (STAT) 3 and GATA binding protein 3 (GATA-3) protein levels. By regulating AR-induced inflammatory reaction and autoimmune response, HE also relieved OVA-induced AR. Thus, HE could be used as a potential drug to treat AR.

Paeonol attenuates airway inflammation and hyperresponsiveness in a murine model of ovalbumin-induced asthma

2010 ◽  
Vol 88 (10) ◽  
pp. 1010-1016 ◽  
Author(s):  
Qiang Du ◽  
Gan-Zhu Feng ◽  
Li Shen ◽  
Jin Cui ◽  
Jian-Kang Cai
Keyword(s):  
Bronchoalveolar Lavage ◽  
Airway Inflammation ◽  
Bronchoalveolar Lavage Fluid ◽  
Immunoglobulin E ◽  
Therapeutic Potential ◽  
Lavage Fluid ◽  
Interleukin 4 ◽  
Moutan Cortex ◽  
Ifn Γ ◽  
Anti Inflammatory

Paeonol, the main active component isolated from Moutan Cortex, possesses extensive pharmacological activities such as anti-inflammatory, anti-allergic, and immunoregulatory effects. In the present study, we examined the effects of paeonol on airway inflammation and hyperresponsiveness in a mouse model of allergic asthma. BALB/c mice sensitized and challenged with ovalbumin were administered paeonol intragastrically at a dose of 100 mg/kg daily. Paeonol significantly suppressed ovalbumin-induced airway hyperresponsiveness to acetylcholine chloride. Paeonol administration significantly inhibited the total inflammatory cell and eosinophil count in bronchoalveolar lavage fluid. Treatment with paeonol significantly enhanced IFN-γ levels and decreased interleukin-4 and interleukin-13 levels in bronchoalveolar lavage fluid and total immunoglobulin E levels in serum. Histological examination of lung tissue demonstrated that paeonol significantly attenuated allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells in the airway. These data suggest that paeonol exhibits anti-inflammatory activity in allergic mice and may possess new therapeutic potential for the treatment of allergic bronchial asthma.

High-mobility group box-1 protein induce inflammatory response after pulmonary injury

2015 ◽  
Vol 3 (3) ◽  
pp. 195-214
Author(s):  
Jingxian H Golemis ◽  
Laurie J Rudensky
Keyword(s):  
Lung Injury ◽  
Inflammatory Response ◽  
Intratracheal Instillation ◽  
High Mobility ◽  
Lavage Fluid ◽  
High Mobility Group ◽  
Saline Control ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Chromosomal Protein

High-mobility group box 1 (HMGB1), a highly conserved non-histone chromosomal protein, was found to act as a potent proinflammatory cytokine and a mediator that participated in the development of systemic inflammatory response. Forty wild type C57BL/6 male (25-30gms) mice were randomly divided into three groups: saline control group; anti-HMGB1 antibody treated group and untreated group. Each group received intratracheal instillation twice per week for 4 consecutive months. 24 hours after the last exposure, anaesthetize the mice with chloral hydrate, bronchoalveolar lavage fluid was collected for cytokines analysis were measured by enzyme linked immunosorbent assay (ELISA). The level of the HMGB1 in lung tissue was determined by real-time PCR and western blot. Lung were fixed with 4% paraformaldehyde for histopathological detection. The serum level of HMGB1 increased after lung injury [peaked 2-5 hr] after lung injury, furthermore this upregulation in HMGB1 associated with increased proinflammatory cytokines [TNF-α, IL-6, IL-1β]. The injection of anti-HMGB1 antibody suppressed inflammatory reaction and improved the survival rate compared with control mice [71.3% vs. 29.4% P=0.031]

Circulating T helper 17 and IFN-γ positive Th17 cells in Major Depressive Disorder

2020 ◽  
Vol 394 ◽  
pp. 112811
Author(s):  
Raghumoy Ghosh ◽  
PVSN Kiran Kumar ◽  
Prasenjit Mitra ◽  
Purvi Purohit ◽  
Naresh Nebhinani ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Th17 Cells ◽  
T Helper ◽  
T Helper 17 ◽  
Major Depressive ◽  
Ifn Γ

Antidepressant Drug, Desipramine, Alleviates Allergic Rhinitis by Regulating Treg and Th 17 Cells

2013 ◽  
Vol 26 (1) ◽  
pp. 107-115 ◽  
Author(s):  
Y. Zhang ◽  
H. Zhen ◽  
W. Yao ◽  
F. Bian ◽  
X. Mao ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Immunoglobulin E ◽  
Antidepressant Drug ◽  
Flow Cytometric Analysis ◽  
Specific Ige ◽  
Tricyclic Antidepressant ◽  
Interleukin 4 ◽  
Therapeutic Effects ◽  
Nasal Symptoms ◽  
Ifn Γ

Allergic rhinitis (AR) is characterized by IgE-mediated immediate hypersensitivity and usually progresses to chronic nasal inflammation, with depression as one of its comorbidities. The importance of treating the depression in AR patients has been increasingly recognized. Desipramine is a representative of tricyclic-antidepressant agents. In the present study we investigate whether desipramine has therapeutic effects on AR inflammation. BALB/C mice were sensitized by intraperitoneal injection of ovalbumin (OVA), followed by repeated challenge with OVA intranasally. Desipramine was administered orally to treat the mice. The nasal symptoms (sneezing, nasal scratching etc.) of AR were evaluated to determine the severity of AR. Cytokines in the nasal lavage fluid (NALF), including interferon-γ (IFN-γ), interleukin 4 (IL-4) and serum OVA-specific immunoglobulin E (IgE) antibody were measured by ELISA. The regulatory T cells (Treg) and T helper cells 17 (Th17) were quantified by flow cytometric analysis. As a result, the repeated oral administration of desipramine attenuated the nasal symptoms (sneezing and nasal rubbing) in AR mice. Desipramine also suppressed the serum OVA-specific IgE and IL-4 levels, but had no effect on IFN-γ level. Moreover, desipramine treatment up regulated CD4+CD25+Foxp3+Treg cells, which were found down-regulated in established AR mice. Meanwhile, desipramine administration attenuated CD4+IL-17+ Th17 cells, which were significantly increased in AR mice. These results suggest that the antidepressant drug, desipramine, also has anti-allergic action, which was possibly achieved by reducing allergen-specific IgE and Th2 cytokine production and maintaining a balance between Treg and Th17 cells. Thus, this study provide the first evidence that desipramine may be utilized to treat allergic diseases, especially for those allergic patients with depression or depression patients with allergy.

Effect of Astragalus membranaceus in Ovalbumin-Induced Allergic Rhinitis Mouse Model

2019 ◽  
Vol 33 (4) ◽  
pp. 420-432
Author(s):  
Zhong Bing ◽  
Du Jin-Tao ◽  
Liu Feng ◽  
Luo Ba ◽  
Liu Ya-Feng ◽  
...  
Keyword(s):  
T Cells ◽  
Allergic Rhinitis ◽  
Nasal Mucosa ◽  
Lymphoid Tissue ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Binding Activity ◽  
Dna Binding Activity ◽  
Nasal Lavage Fluid ◽  
Ifn Γ

Background Astragalus membranaceus (AM), a traditional Chinese medicine, has been used to treat allergic diseases, but the mechanism for treating allergic rhinitis (AR) remains unclear. Objective The purpose of this study was to look at the anti-inflammatory effect of AM on AR and the mechanism of anti-allergy. Methods The mouse model of AR was induced by ovalbumin. Allergic symptoms, number of eosinophils in nasal mucosa, and levels of inflammatory cells in nasal lavage fluid were analyzed. We explored the serum immunoglobulin E (IgE), interleukin-4 (IL-4), IL-5, IL-13, interferon-γ (IFN-γ), and IL-10. Besides, the relative mRNA of IL-4, IL-5, and IL-13 was also detected in nasal mucosa tissue. The proportion of CD4+ CD25+ Foxp3+ T cells in the spleen and nasal lymphoid tissue were analyzed. The mRNA levels of nuclear factor-kappa B p65 (NF-κB p65) and inhibitory kappa B alpha (IκBα), as well as NF-κB p65 DNA binding activity, were tested. We also measured the protein levels of NF-κB p65 and p-NF-κB p65 in nasal mucosa. Results AM could reduce the number of eosinophils in the nasal mucosa and decrease the levels of inflammatory cells in nasal lavage fluid. The serum IgE, IL-4, IL-5, and IL-13 were also decreased, while levels of IFN-γ and IL-10 were increased. The relative mRNA of IL-4, IL-5, and IL-13 was decreased by AM. AM increased the proportion of CD4+ CD25+ Foxp3+ T cells in the spleen and nasal lymphoid tissue. In addition, AM could reduce the activity of NF-kB by inhibiting the mRNA expression and DNA binding activity of NF-κB p65. However, AM had no significant effect on mRNA of IκBα. Above all, AM could reduce the p-NF-κB p65 protein expression of nasal mucosa. Conclusions AM could reduce the secretion of inflammatory cytokines by increasing the level of CD4+ CD25+ Foxp3+ T cells and inhibiting the activation of the NF-κB.

IL-36α contributes to enhanced T helper 17 type responses in allergic rhinitis

Cytokine ◽  
2020 ◽  
Vol 128 ◽  
pp. 154992
Author(s):  
Xiaowei Qin ◽  
Tianhong Zhang ◽  
Chunrui Wang ◽  
Huijun Li ◽  
Ming Liu ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
T Helper ◽  
T Helper 17

scholarly journals MicroRNA-29 mediates anti-inflammatory effects and alleviation of allergic responses and symptoms in mice with allergic rhinitis

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Jia Wang ◽  
Jinshu Yin ◽  
Hong Peng ◽  
Aizhu Liu
Keyword(s):  
Allergic Rhinitis ◽  
Nasal Mucosa ◽  
Immunoglobulin E ◽  
Underlying Mechanism ◽  
Lavage Fluid ◽  
Specific Ige ◽  
Ar Model ◽  
Protein Levels ◽  
Mucosa Cell

Abstract Background To investigate the role of microRNA-29 (miR-29) in mice with allergic rhinitis (AR) and its underlying mechanism. Methods AR model was established in BALB/c mice by intraperitoneal sensitization and intranasal challenge with ovalbumin (OVA). miRNA expression was examined in the nasal mucosa tissues of mice and patients with AR, and miRNA-29 was found to be downregulated. To unveil the role of miRNA-29 in AR, it was overexpressed in the nasal mucosa of AR mice by intranasal administration of miRNA-29 agomir. The symptoms of nasal rubbing and sneezing were recorded and evaluated. miR-29 expression, OVA-specific immunoglobulin E (IgE) concentration, pro-inflammatory cytokines levels, eosinophils number, and cleaved caspase-3 and CD276 expression were examined in nasal mucosa tissues and nasal lavage fluid (NALF) by qRT-PCR, ELISA, hematoxylin and eosin staining, western blotting, or immunohistochemistry, respectively. TUNEL assay was used to analyze nasal mucosa cells apoptosis. Results Decreased expression of miR-29 was observed in AR, the symptoms of which were alleviated by overexpressing miR-29. In addition, overexpression of miR-29 markedly reduced the concentration of OVA-specific IgE, the levels of IL-4, IL-6, IL-10, and IFN-γ, the pathological alterations and eosinophils infiltration in the nasal mucosa. Furthermore, restoration of miR-29 expression reduced nasal mucosa cell apoptosis. Moreover, overexpression of miR-29 significantly attenuated CD276 mRNA and protein levels in nasal mucosa cells. Conclusion MiR-29 mediated antiallergic effects in OVA-induced AR mice by decreasing inflammatory response, probably through targeting CD276. MiRNA-29 may serve as a potential novel therapeutic target for the treatment of AR.

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