Effects of Ursolic Acid on the Expression of Th1–Th2-related Cytokines in a Rat Model of Allergic Rhinitis After PM2.5 Exposure

2020 ◽  
Vol 34 (5) ◽  
pp. 587-596 ◽  
Author(s):  
Na Sun ◽  
Zhijin Han ◽  
Hong Wang ◽  
Zhiqiang Guo ◽  
Congrui Deng ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Particulate Matter ◽  
Ursolic Acid ◽  
Nasal Mucosa ◽  
Rat Model ◽  
Ar Model ◽  
Eosinophilic Infiltration ◽  
Th2 Cytokines ◽  
Nasal Symptoms ◽  
Pm2.5 Exposure

Background Allergic rhinitis (AR) is a global health problem and closely related to environmental factors. Ursolic acid (UA) has potential in the treatment of allergic inflammation. The effects of UA intervention on PM2.5-induced AR remain uncertain. Objective To assess the effects of UA on nasal symptoms and the expression of T-helper (Th)1–Th2-related cytokines in a rat model of AR after fine particulate matter (particulate matter ≤ 2.5 µm [PM2.5]) exposure. Methods A total of 40 healthy female Sprague-Dawley rats were randomly divided into 4 groups: normal control group (NC group), ovalbumin (OVA)- induced AR model (AR group), PM2.5-exposed AR group exposed to 200 g/m3 PM2.5 for 30 days via inhalation (ARE group), and a group with UA intervention to the AR model after PM2.5 exposure (UA group). UA intervention was adopted after PM2.5 exposure in the UA group. Nasal symptoms and levels of Th1–Th2 cytokines in the serum were detected in each individual rat. The pathological changes and expression of Eotaxin in the nasal mucosa of each individual rat were examined by histology. Results PM2.5 significantly increased the number of sneezes and nasal rubs in the rats with AR, and UA alleviated these symptoms. UA decreased interleukin (IL)-4, IL-5, IL-13, Eotaxin-1, and OVA Immunoglobulin E (IgE) protein levels. In the AR group, hematoxylin and eosin staining showed disordered arrangement of the nasal mucosa epithelium, cell shedding, eosinophilic infiltration, swelling of the glands, and submucosal vascular congestion. UA group showed reduced eosinophilic infiltration and orderly arrangement of the mucosal epithelium when compared with the ARE group. Immunohistochemical results showed that the expression of Eotaxin in the UA group was lower than that in the ARE group. Conclusion UA could relieve nasal symptoms caused by PM2.5 exposure, the possible mechanism of which is to inhibit the expression of Th2 cytokines, eosinophilic infiltration, and specific IgE production.

Ursolic Acid Alleviates Mucus Secretion and Tissue Remodeling in Rat Model of Allergic Rhinitis After PM2.5 Exposure

2020 ◽  
pp. 194589242095335
Author(s):  
Na Sun ◽  
Congrui Deng ◽  
Qianbiao Zhao ◽  
Zhijin Han ◽  
Zhiqiang Guo ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Particulate Matter ◽  
Ursolic Acid ◽  
Nasal Mucosa ◽  
Rat Model ◽  
Tissue Remodeling ◽  
Collagen Deposition ◽  
Exposure System ◽  
Mucus Hypersecretion ◽  
Pm2.5 Exposure

Background According to recent epidemiologic studies, exposure to fine particulate matter (particulate matter 2.5 ≤ µm [PM2.5]) in the air increases the incidence and severity of allergic rhinitis (AR). Ursolic acid (UA) has activities in immune regulation and anti-inflammatory. However, the role of UA intervention on PM2.5-exposed AR remains unknown. In this study, we investigated the effects of UA on tissue remodeling and mucus hypersecretion in a rat model of AR after PM2.5 exposure. Methods AR was induced in rats with ovalbumin (OVA) and they were exposed to ambient PM2.5(200 µg/m3) via a PM2.5 inhalation exposure system for 30 days(ARE group). Ursolic acid intervention was administrated in the AR model after PM2.5 exposure (UA group). Hyperplasia of goblet cells was detected by periodic acid-Schiff (PAS) staining and collagen deposition in the nasal mucosa was detected by Masson trichrome (MT) staining.MUC5AC expression was measured by immunohistochemistry. Results UA group showed reduced goblet cell hyperplasia and collagen deposition in the nasal mucosa which exacerbated after PM2.5 exposure, as reflected by PAS and MT staining when compared with the ARE group. Immunohistochemical results showed that the expression of MUC5AC in the UA group was lower than that in the ARE group. Conclusion Analysis of our data indicated that UA could attenuate nasal remodeling and mucus hypersecretion in aggravation of AR after PM2.5 exposure, which may be the pathophysiologic mechanisms for the prevention of AR exacerbated by exposure to PM2.5.

T-Helper Type 1-T-Helper Type 2 Shift and Nasal Remodeling after Fine Particulate Matter Exposure in a Rat Model of Allergic Rhinitis

2017 ◽  
Vol 31 (3) ◽  
pp. 148-155 ◽  
Author(s):  
Zhi-Qiang Guo ◽  
Wei-Yang Dong ◽  
Jian Xu ◽  
Zhi-Cong Hong ◽  
Ren-Wu Zhao ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Particulate Matter ◽  
Rat Model ◽  
Fine Particulate Matter ◽  
Ar Model ◽  
Th2 Cytokines ◽  
Collagen Deposition ◽  
T Helper ◽  
Fine Particulate ◽  
Helper Type

Background Exposure to fine particulate matter (particulate matter ≤2.5 μm [PM2.5]) increases the risk of allergic rhinitis (AR), but the underlying mechanisms remains unclear. Thus, we investigated the roles of T-helper (Th)1–Th2 cytokines and nasal remodeling after ambient PM2.5 exposure in a rat model of AR. Methods Female Sprague-Dawley rats were randomized into six groups: a negative control group, a group of healthy rats exposed to 3000 μg/m3 PM2.5, an ovalbumin (OVA) induced AR model, and three PM2.5-exacerbated AR groups exposed to three different concentrations (200, 1000, and 3000 μg/m3) of PM2.5 for 30 days via inhalation. Nasal symptoms, levels of Th1–Th2 cytokines, the degree of eosinophilia in nasal lavage fluid (NLF), and the messenger RNA (mRNA) expressions of transcription factors GATA-3 and T-bet in the nasal mucosa were measured in each individual rat. Hyperplasia of globet cells and collagen deposition were examined by histology. Results PM2.5 significantly increased the number of sneezes and nasal rubs in rats with AR. PM2.5 also significantly decreased interferon gamma and increased interleukin (IL) 4 and IL-13 expressions as well as the number of eosinophils in NLF. The mRNA expression of GATA-3 in the nasal mucosa of rats with AR was upregulated by PM2.5, whereas T-bet was significantly downregulated. Statistically significant differences in OVA-specific serum immunoglobulin E, goblet cell hyperplasia, collagen deposition, and transforming growth factor beta 1 levels were observed between the PM2.5-exacerbated AR groups and the AR model group. Conclusion Analysis of our data indicated that an increase in the immune response with Th2 polarization and the development of nasal remodeling may be the immunotoxic mechanisms behind the exacerbation of AR after exposure to PM2.5.

miR-338–3p inhibits autophagy in a rat model of allergic rhinitis after PM2.5 exposure through AKT/mTOR signaling by targeting UBE2Q1

2021 ◽  
Vol 554 ◽  
pp. 1-6
Author(s):  
Jin-Chao Wang ◽  
Yu Huang ◽  
Ru-Xin Zhang ◽  
Zhi-Jin Han ◽  
Ling-Ling Zhou ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Rat Model ◽  
Mtor Signaling ◽  
Pm2.5 Exposure

scholarly journals The extract of black cumin, licorice, anise, and black tea alleviates OVA-induced allergic rhinitis in mouse via balancing activity of helper T cells in lung

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Chengsong Liao ◽  
Yangyang Han ◽  
Zhijing Chen ◽  
Huricha Baigude
Keyword(s):  
Allergic Rhinitis ◽  
Nasal Mucosa ◽  
Aqueous Extract ◽  
Nigella Sativa ◽  
Inflammatory Cells ◽  
Serum Levels ◽  
Lavage Fluid ◽  
Ar Model ◽  
Control Group ◽  
Black Cumin

Abstract Background A formulation of black cumin (Nigella sativa L.), licorice (Glycyrrhiza glabra L.), anise (Pimpinella anisum L.) and tea (Camellia sinensis (L.) Kuntze) (denoted BLAB tea) is traditionally used to relief allergy reaction including allergic rhinitis. However, little is known about its underlining mechanism of anti-allergic effects. Methods To investigate the anti-allergenic mechanism of BLAB tea, we treated ovalbumin (OVA)-induced allergic rhinitis (AR) model of mice with BLAB tea, and elucidated its possible mechanism of action. Mice in the control group were treated with phosphate-buffered saline only. Subsequently, the infiltration of different inflammatory cells was measured. In addition, histopathological changes in the nasal mucosa, and the levels of allergen-specific cytokines and OVA-specific immunoglobulins were measured. Results The aqueous extract of BLAB significantly alleviated the nasal symptoms and reduced the accumulation of inflammatory cells in the nasal mucosa and nasal lavage fluid of AR model of mice. Conclusion The aqueous extract of BLAB induced the production of Th1 and Treg cytokines and inhibited the release of Th2 cytokines and histamine in nasal mucosa and serum of mice while decreasing the serum levels of OVA-specific IgE, IgG1, and IgG2a. These results suggest the potential of the aqueous extract of BLAB as a treatment option for allergic diseases.

scholarly journals Taurine Promotes the Production of CD4+CD25+FOXP3+ Treg Cells through Regulating IL-35/STAT1 Pathway in a Mouse Allergic Rhinitis Model

2020 ◽  
Author(s):  
Jing Zhou ◽  
Yi Lu ◽  
Wei Wu ◽  
Yunhai Feng
Keyword(s):  
Allergic Rhinitis ◽  
Nasal Mucosa ◽  
Goblet Cell ◽  
Inflammatory Cytokine ◽  
Neutralizing Antibody ◽  
Treg Cells ◽  
Ar Model ◽  
Cytokine Release ◽  
Cell Content ◽  
Taurine Treatment

Abstract Background: Allergic rhinitis (AR) is one of the most widespread immune conditions worldwide. However, common treatments often present with significant side effects or are cost-prohibitive for much of the population. A plethora of treatments have been used for the treatment of AR including antihistamines, steroids, and immune modulators. Among the treatments which have shown potential for efficacy in treating AR with a minimum of side effects but remains understudied is the conditionally essential amino acid taurine. Taurine has been previously shown to reduce AR symptoms. Here, we examine the role of taurine in modulating T regulatory cells, modulating the cytokine response in AR, and restoring healthy nasal mucosa.Methods: Blood samples from 20 healthy donors and 20 AR patients were compared for CD4+CD25+FoxP3+ T regulatory (Treg) cell population percentage, cytokine release, and STAT1 signaling with and without taurine treatment or IL-35 neutralization. An OVA-induced AR mouse model was administered vehicle, taurine, or taurine plus an IL-35 neutralizing antibody and assayed for sneezing frequency, inflammatory cytokine response, nasal mucosa goblet cell density, and T regulatory cell percentage. CD4+ cells were further examined for cytokine release, STAT1 phosphorylation, and response to an anti-IL-35 antibody with and without a STAT1 inhibitor. Results: Comparison of blood from normal donors and AR patients showed a reduction in CD4+CD25+FoxP3+ Treg cells in AR patients and a strong correlation between Treg percentage and IL-35 release. A similar pattern of Treg suppression was found in untreated AR mice when compared to normal control mice wherein there was a reduction in Treg percentage and a corresponding decrease in IL-35 release. AR mice also demonstrated increased sneezing frequency, an infiltration of goblet cell in nasal mucosa, and a reduction in IL-35 release from CD4+ cells. Conversely, IL-4, IL-5, and IL-13 secretion from CD4+ cells were increased in AR model mice, as was STAT1 phosphorylation. When AR mice were treated with taurine, sneezing frequency and nasal mucosa goblet cell content were reduced while Treg abundance was increased to that of normal mice. Accordingly, IL-35 release was restored, while IL-4, IL-5, and IL-13 secretion from CD4+ cells were suppressed. Likewise, STAT1 phosphorylation was inhibited with taurine treatment. Taurine-treated mice also given an IL-35 neutralizing antibody exhibited AR pathology including frequent sneezing and high nasal goblet cell content while retaining a restoration of Tregs. Furthermore, murine AR model CD4+ cells exposed to recombinant IL-35 responded with a reduction in inflammatory cytokine release and a decrease in STAT1 phosphorylation, mimicking the effect of taurine treatment. Conclusions: Taurine induces release of IL-35 in AR; IL-35 promotes the production of CD4+CD25+FoxP3+ Treg cells via a STAT1-dependent pathway. The restoration of Treg populations by taurine normalizes the inflammatory response, reduces AR symptomology, and reduces histopathologic signs of AR.

Combined Treatment With H1 and H4 Receptor Antagonists Improves Th2 Inflammatory Responses in the Nasal Mucosa of Allergic Rhinitis Rats

2021 ◽  
pp. 194589242110026
Author(s):  
Weiwei Wang ◽  
Hongwei Yu ◽  
Yongliang Pan ◽  
Shengwen Shao
Keyword(s):  
Allergic Rhinitis ◽  
Nasal Mucosa ◽  
Inflammatory Responses ◽  
Combined Treatment ◽  
Interleukin 4 ◽  
Therapeutic Effects ◽  
Th2 Cytokines ◽  
Receptor Antagonists ◽  
Mhc Ii ◽  
H4 Receptor

Background Histamine H1 receptor (H1R) antagonists are the first-line drugs for the treatment of allergic rhinitis (AR) at present. Emerging evidence supports an important role of histamine H4 receptor (H4R) in allergic diseases. However, information regarding the effects of combined treatment with H1 and H4 receptor antagonists in AR is limited. Objectives We aimed to assess the effects of combined treatment with H1R and H4R antagonists on Th2 inflammatory responses in the nasal mucosa of AR rats. Methods Sprague Dawley rats were sensitized with ovalbumin and treated with H1R antagonist desloratadine or/and H4R antagonist JNJ7777120. Western blotting was used to assay the phenotypic markers of mature dendritic cells in the nasal mucosa, including major histocompatibility complex class II (MHC-II) and co-stimulatory molecules CD80, CD86 and OX40 ligand (OX40L). Th2 inflammatory cytokines including interleukin-4, 5 and 13 in nasal lavage fluids were determined by using enzyme-linked immunoassay. Results The treatment with desloratadine alone down-regulated the CD86 expression, and decreased the production of Th2 cytokines, but had no impact on the expression of MHC-II, CD80 and OX40L. The administration of NJ7777120 alone reduced the levels of CD86, OX40L and Th2 cytokines, whereas MHC-II and CD80 expression was unaffected. The combination of desloratadine and JNJ7777120 showed more significant synergistic therapeutic effects than monotherapy. Conclusion H4R antagonist acted synergistically with H1R antagonist to reduce Th2 inflammatory responses by down-regulating CD86 and OX40L expression in the nasal mucosa of AR rats. The combination with H1R and H4R antagonists might be a new strategy for AR treatment.

scholarly journals D-Pinitol Attenuated Ovalbumin-induced Allergic Rhinitis in Experimental Mice Via Balancing Th1/Th2 Response

2021 ◽  
Author(s):  
Xiying You ◽  
Xiaopeng Sun ◽  
Junfei Kong ◽  
Jifeng Tian ◽  
Yanping Shi ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Immune Responses ◽  
Nasal Mucosa ◽  
Potential Effect ◽  
Ar Model ◽  
Cytokine Signaling ◽  
Control Group ◽  
Th2 Response ◽  
T Box ◽  
Th1 Immune Responses

Allergic rhinitis (AR) is a complex, chronic immunoinflammatory disorder of the membrane lining of the nasal mucosa. D-Pinitol is considered a cyclic polyol with a potential effect against various allergies. In the present study, we evaluated the anti-allergic effect of pinitol on ovalbumin (OVA)-induced AR model in mice. BALB/c mice were initially sensitized with an intraperitoneal injection of OVA and divided into 5 groups (n=18, in each group) for a treating schedule of distilled water (DW), montelukast (10 mg/kg), and pinitol (5, 10, and 20 mg/kg) through the mouth. Two saline-injected groups were considered as controls by orally administrating DW and pinitol 20. Thereafter, test and control groups were intranasally challenged by OVA and saline, respectively. Our results showed that the OVA challenge caused a marked elevation in AR symptoms like nasal rubbing, sneezing, and discharge which were remarkably diminished using pinitol (10 and 20 mg/kg) and the results were comparable with montelukast. Additionally, increased levels of total and OVA-specific serum Immunoglobulin (Ig) E and IgG1 were significantly attenuated by pinitol as compared to the control group but not the montelukast group. In AR-induced mice, pinitol had significant modulatory effects on representative markers of Th2 (GATA binding protein 3), signal transducer and activator of transcription-6, Interleukins (IL)-4, IL-5, IL-13, suppressors of cytokine signaling 1, Toll-like receptor 4, and myeloid differentiation factor 88), and Type 1 T helper (Th1) immune responses (T-box protein expressed in T cells and Interferon-gamma) as well as the histopathological aberrations induced in the nasal mucosa. In conclusion, Pinitol had potential effects on OVA-induced AR mice through amelioration of nasal symptoms and balancing the Th1/Th2 immune responses during the allergic rhinitis condition.

scholarly journals Anti-Interleukin-1 Beta/Tumor Necrosis Factor-Alpha IgY Antibodies Reduce Pathological Allergic Responses in Guinea Pigs with Allergic Rhinitis

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Hu Wei-xu ◽  
Zhou Wen-yun ◽  
Zhu Xi-ling ◽  
Wen Zhu ◽  
Wu Li-hua ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Treatment Group ◽  
Nasal Mucosa ◽  
Guinea Pigs ◽  
Interleukin 1 ◽  
Allergic Inflammation ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Ar Model ◽  
Necrosis Factor Alpha

This study aims to determine whether the combined blockade of IL-1βand TNF-αcan alleviate the pathological allergic inflammatory reaction in the nasal mucosa and lung tissues in allergic rhinitis (AR) guinea pigs. Healthy guinea pigs treated with saline were used as the healthy controls. The AR guinea pigs were randomly divided into (1) the AR model group treated with intranasal saline; (2) the 0.1% nonspecific IgY treatment group; (3) the 0.1% anti-TNF-αIgY treatment group; (4) the 0.1% anti-IL-1βIgY treatment group; (5) the 0.1% combined anti-IL-1βand TNF-αIgY treatment group; and (6) the fluticasone propionate treatment group. The inflammatory cells were evaluated using Wright’s staining. Histopathology was examined using hematoxylin-eosin staining. The results showed that the number of eosinophils was significantly decreased in the peripheral blood, nasal lavage fluid, and bronchoalveolar lavage fluid (P<0.05), and eosinophil, neutrophil, and lymphocyte infiltration and edema were significantly reduced or absent in the nasal mucosa and lung tissues (P<0.05) in the combined 0.1% anti-IL-1β- and TNF-αIgY-treated guinea pigs. The data suggest that topical blockade of IL-1βand TNF-αcould reduce pathological allergic inflammation in the nasal mucosa and lung tissues in AR guinea pigs.

scholarly journals Denervation of nasal mucosa induced by posterior nasal neurectomy suppresses nasal secretion, not hypersensitivity, in an allergic rhinitis rat model

2016 ◽  
Vol 96 (9) ◽  
pp. 981-993 ◽  
Author(s):  
Hironobu Nishijima ◽  
Kenji Kondo ◽  
Makiko Toma-Hirano ◽  
Shinichi Iwasaki ◽  
Shu Kikuta ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Nasal Mucosa ◽  
Rat Model ◽  
Nasal Secretion

Effect of PM2.5 on MicroRNA Expression and Function in Nasal Mucosa of Rats With Allergic Rhinitis

2020 ◽  
Vol 34 (4) ◽  
pp. 543-553
Author(s):  
Yu Huang ◽  
Zhi-Qiang Guo ◽  
Ru-Xin Zhang ◽  
Ren-Wu Zhao ◽  
Wei-Yang Dong ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Nasal Mucosa ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Mirna Gene ◽  
Ar Model ◽  
Qrt Pcr ◽  
Mirna Expression Profiles ◽  
Differentially Expressed Mirnas ◽  
And Function

Background Particulate matter 2.5 (PM2.5) refers to particulate matter with aerodynamic equivalent diameter less than or equal to 2.5 µm, which is an important component of air pollution. PM2.5 aggravates allergic rhinitis (AR) and promotes AR nasal mucosa inflammation. Therefore, the influence of PM2.5 inhalation exposure on microRNA (miRNA) expression profiles and function in the nasal mucosa of AR rats was investigated. Methods Female Sprague Dawley rats were distributed randomly to 2 groups: AR model PM2.5 exposure group (ARE group) and AR model PM2.5-unexposed control group (ARC group). The rats of ARE group were made to inhale PM2.5 at a concentration of 200 µg/m3, 3 h/day, for 30 days. miRNA expression profiles of the nasal mucosa from both groups were determined using an miRNA gene chip and were verified by quantitative real-time PCR (qRT-PCR). Gene function enrichment analysis was performed using bioinformatics analysis. Results The ARE group revealed 20 significantly differentially expressed miRNAs, including 4 upregulated and 16 downregulated miRNAs (fold change > 1.5 or < 0.66, P < .05). Of these, 9 selected miRNAs were verified by qRT-PCR, and the results of 8 miRNAs were in accordance with the miRNA gene chip results, with highly positive correlation ( r = .8583, P = .0031). Numerous target genes of differentially expressed miRNAs were functionally enriched in high-affinity immunoglobulin E receptor signaling, ErbB signaling, mucin O-glycans biosynthesis, transforming growth factor β signaling, mitogen-activated protein kinase signal transduction, phosphatidylinositol signaling, mucopolysaccharide biosynthesis, mammalian target of rapamycin signaling, T cell receptor signaling, Wnt signaling, chemokine signal transduction, and natural killer cell-mediated cytotoxicity pathways. Conclusions PM2.5 causes significant changes in miRNA expression in the nasal mucosa of AR rats. miRNA plays an important role in regulating PM2.5 effects in AR rat biological behavior and mucosal inflammation. This study provides a theoretical basis for the prevention and treatment of AR from the effects of environmental pollution on the gene regulation mechanism.

Sign in / Sign up

Export Citation Format

Share Document