OVA-induced Allergic Rhinitis Mice Research Articles

Knockdown of DDX3Y alleviates ovalbumin-induced allergic rhinitis in mice by regulating NF-κB pathway.

Allergic rhinitis (AR), a type of chronic inflammatory disease that exists in the nasal mucosa, significantly impacts the quality of life. DDX3Y gene encodes an RNA helicase belonging to the DEAD-box protein family and is part of the DDX3 subfamily that affects the progression of multiple diseases. However, the specific role and mechanisms of DDX3Y in AR remain unclear. This study investigates the effects of DDX3Y knockdown on ovalbumin (OVA)-induced AR in mice. We found that DDX3Y is highly expressed in the nasal mucosa of AR mice. Knockdown of DDX3Y in OVA-induced AR mice significantly alleviated nasal manifestations, reduced immunoglobulin E and histamine levels, and improved nasal mucosal histopathology. Additionally, knockdown of DDX3Y suppressed secretion of inflammatory factor nuclear factor kappa B (NF-κB) phosphorylation, thereby mitigating local inflammatory responses. These findings suggested that targeting DDX3Y could offer a novel therapeutic strategy for managing AR by modulating the NF-κB pathway.

GBP2 Regulates Lipid Metabolism by Inhibiting the HIF-1 Pathway to Alleviate the Progression of Allergic Rhinitis.

Allergic rhinitis (AR) is a prevalent allergic disorder instigated by a variety of allergenic stimuli. The study aims to elucidate the mechanistic underpinnings of Guanylate-binding protein 2 (GBP2) in modulating AR. Bioinformatics analysis was used to identify hub genes in AR, and GBP2 was identified. Mice were injected with ovalbumin (OVA) to create AR model. The pathological changes of the nasal mucosa were observed by hematoxylin-eosin staining. ELISA and western blot demonstrated that in OVA-induced AR mice, high IgE and IgG1 levels, inflammation (increased TNF-α, IL-5 and IFN-γ), oxidative stress (high ROS, low TAOC and GSH) and abnormal lipid metabolism (increased TC and LDL-C, decreased HLD-C) were observed. Mouse nasal mucosal epithelial cells (MNECs) were treated with TNF-α to simulate AR. Cell viability and apoptosis were evaluated by CCK-8 assay and flow cytometer, respectively. In vitro assay revealed that GBP2 inhibited total IgE, OVA-IgE and IgG1 levels and suppressed abnormal lipid metabolism, inflammation and oxidative stress to alleviate AR. Furthermore, HIF-1 pathway was screened as the downstream pathway of GBP2. GBP2 inhibited the HIF-1 pathway, and Fenbendazole-d3, the activator of HIF-1 pathway, weakened the inhibitory effects of GBP2 on apoptosis, inflammation, oxidative stress and abnormal lipid metabolism in vitro. In summary, GBP2 alleviated abnormal lipid metabolism, inflammation and oxidative stress by inhibiting the HIF-1 pathway, providing a direction for the treatment of AR.

Prevention and alleviation of allergic rhinitis by oral administration of Lacticaseibacillus paracasei GOLDGUT-Lpc969.

Allergic rhinitis (AR) is a widespread upper airway disorder characterized by inflammation of the nasal passages. It is immunologically mediated via the hypersensitivity type I mechanism, which is primarily elicited by the immunoglobulin E (IgE)-linking allergen-induced imbalance of the Th2/Th1 immune response. Owing to the limited efficacy of current medications, probiotics have received attention for their potential in preventing and ameliorating AR. In this study, a Lacticaseibacillus paracasei strain, GOLDGUTLpc969 (Lpc969), isolated from the feces of healthy adults, was proven to be effective in preventing AR by LPA-induced RBL-2H3 in-vitro and OVA-induced AR mice in-vivo evaluation. The strain significantly attenuated the release of histamine and degranulation in LPS-induced RBL-2H3 cells. In the OVA-induced AR mice, L. paracasei GOLDGUT-Lpc969 also exhibited a significant decrease in disease indicators such as the disease activity index (DAI score), serum IgE, and serum histamine. Treatment with L. paracasei GOLDGUT-Lpc969 led to significant suppression of the Th2-related cytokines IL-4, IL-5, IL-6, IL-13, and TNF-α in the serum of mice. Furthermore, a comparison of the genomes of three previously reported AR-effective L. paracasei strains (including GOLDGUTLpc969) and one non-effective L. paracasei strain revealed that the gene K03671 may play a key role in alleviating AR symptoms. In conclusion, this study highlights the efficacy of L. paracasei GOLDGUT-Lpc969 in AR prevention by suppressing the Th2 immune response and proposes the potential involvement of the functional gene K03671 in ameliorating AR symptoms. Therefore, L. paracasei GOLDGUT-Lpc969 shows promise as a probiotic for preventing AR.

Changes in respiratory tract and gut microbiota in AR mice and their relationship with Th1/Th2/Treg

BackgroundThe etiology of allergic rhinitis (AR) is not fully understood. Studies have shown that the maturation of children's immune systems is closely related to microecology. However, few studies have focused simultaneously on changes in respiratory and gut microbiota in AR and their correlation between microecological changes and Th1/Th2/Treg. ObjectiveThe aim is to investigate the pathogenesis of AR based on respiratory microecology, gut microecology, and Th1/Th2/Treg levels by applying microbiome techniques and correlation analysis. MethodsStandardized OVA-induced AR mice were established. Serum OVA-sIgE, IL-4, IFN-γ, IL-10 were measured by ELISA, Tregs in lymph nodes were determined by flow cytometry, and the histological characteristics of nasal tissues were evaluated by Hematoxylin & Eosin (H&E). Nasal symptoms were observed to determine the reliability of the AR mouse model. Nasal lavage fluid (NALF) and fecal samples were collected after the last OVA challenge. The composition of respiratory microbiota in NALF and gut microbial in feces samples via 16S rRNA gene sequencing between the two groups, further explored the relationship between microbiota and Th1/Th2/Treg levels. ResultsIn the AR group, the incidence of nose rubbing and sneezing in each mouse was significantly increased compared with the control group (all P < 0.001) and the inflammatory cell infiltration of NALF shows a significant increase in eosinophilic and neutrophilic infiltrates upon the AR group; H&E showed that the nasal mucosa of AR mice infiltration of massive eosinophils cells and neutrophils cells. OVA-sIgE and IL-4 in the AR group were increased (P < 0.01, P < 0.05) and IFN-γ, IL-10 were significantly decreased (P < 0.01, P < 0.05). Tregs showed a downward trend in the AR group, but there was no statistical difference. Compared with the control group, the respiratory microbiota of AR mice did not change significantly, while the gut microbiota changed significantly. In gut microbiota, compared to the control group, Shannon index in the AR group revealed a significant decrease at the genus level (P < 0.01), and Simpson index was significantly increased at all levels (all P < 0.05). PCoA also showed significant differences in beta diversity between the two groups (all P < 0.05). Compared to the control group, Deferribacteres at phylum level, Roseburia, Ruminiclostridium, Anaerotruncus at genus level were significantly decreased in the AR group (all P < 0.05). Spearman's rank correlation showed that OVA-sIgE was positively correlated with Bacteroidetes, Muribaculaceae and Erysipelotrichaceae (all P < 0.05); IL-4 was significantly negatively correlated with Epsilonbacteraeota and Deferribacteres (all P < 0.05). Treg was significantly positively correlated with Patescibacteria, Lachnospiraceae, and Saccharimonadaceae in gut microecology. ConclusionOur results showed that the respiratory microbiota of AR mice was not significantly altered, but the gut microbiota varied significantly and there was a correlation between gut microbiota and Th1/Th2/Treg.

Malvidin From Malva sylvestris L. Ameliorates Allergic Responses in Ovalbumin-Induced Allergic Rhinitis Mouse Model via the STAT6/GATA3 Pathway.

Malva sylvestris L. (commonly known as mallow) has been widely used in traditional Tibetan formulations to treat allergic rhinitis (AR), and malvidin is a key anti-inflammation constituent of this plant. The present study aimed to evaluate the potential therapeutic effect and mechanism of malvidin in an AR mouse model. Malvidin's efficacy was evaluated in an AR mouse model induced by ovalbumin (OVA) sensitization and challenge. The factors, such as nasal symptoms, serum OVA-specific immunoglobulin E (IgE) levels, histological changes in the nasal mucosa, and expressions of Th1, Th2, Th17, and Tregs and their cytokines, were assessed. Western blotting was used to analyze the effect of malvidin on signal transducer and activator of transcription 6 (STAT6) and GATA3 expression levels. Malvidin reduced the allergic symptoms and serum levels of OVA-specific IgE in the AR model. Histological analysis indicated that malvidin alleviates nasal mucosal edema, eosinophil infiltration, and goblet cell proliferation. In addition, it altered the expression of Th1/Th2/Th17-related cytokines, enhanced the Treg population, and reduced Th2-mediated immunity by suppressing the phosphorylation of STAT6 and expression of the GATA3 protein. Malvidin significantly improved allergic symptoms in an OVA-induced AR mouse model by modulating Th1/Th2 immune responses and suppressing the STAT6/GATA3 pathway, indicating its potential as a naturally sourced agent for AR management.

Inhibition of dendritic cell autophagy alleviates the progression of allergic rhinitis by inhibiting Th1/Th2/Th17 immune imbalance and inflammation.

Immune imbalance is a fundamental immunological feature of allergic rhinitis (AR). The autophagy in CD11c+ dendritic cells (DCs), the strongest antigen-presenting cells, was reported to induce the occurrence of AR by facilitating CD4+ T cell immune imbalance and subsequent inflammation. Our study was designed to confirm that inhibition of DC autophagy can alleviate the progression of AR by inhibiting the T cell immune imbalance. The AR mouse model was established by using ovalbumin (OVA). OVA-induced mouse models were then injected intraperitoneally with the autophagy inhibitor Baf-A1. Levels of OVA-specific IgE, PGD2, ECP, LTC4, and Th1/Th2/Th17 cell-related cytokines in serum or nasal lavage fluid (NLF) were examined using the corresponding commercial ELISA kits. Morphological changes in the nasal mucosa were observed by HE staining. Nasal mucosa tissues were collected for western blotting to assess the expression of autophagy markers (LC3, P62, and Beclin 1) in each group of mice. Baf-A1 treatment alleviated the allergic symptoms, mitigated inflammatory immune cell infiltration in the nasal mucosa, decreased IgE, LTC4, ECP, and PGD2 levels in both serum and NLF, impaired CD11c+ DC autophagy, and restored Th1/Th2/Th17 cytokine imbalance in OVA-induced AR mice. Furthermore, Baf-A1 treatment also reversed the immune imbalance of CD4+ T cell subtypes and attenuated Th1/Th2/Th17 cytokine imbalance in vitro. Inhibition of CD11c+ DC autophagy suppressed the immune imbalance of CD4+ T cell subsets and attenuated the subsequent inflammatory response, thereby ameliorating the progression of AR.

Effects of Thymus quinquecostatus Celakovski on Allergic Responses in OVA-Induced Allergic Rhinitis Mice

Allergic rhinitis (AR) is defined allergic disease that is mediated by Th2 cells. Its incidence rate is showing a growing tendency worldwide. Research on traditional medicine for AR is also being increasingly conducted. Thymus quinquecostatus Celakovski (TQ) has been used as an important medicinal and aromatic plant in the world. The purpose of this study was to assess whether TQ can alleviate AR. BALB/c mice were sensitized and challenged with ovalbumin (OVA) to provoke AR. Mice were treated with ethanol extract of TQ at 10 or 100 mg/kg after the intranasal OVA challenge. Their clinical symptoms such as nasal rubbing and sneezing were significantly reduced in the ethanol extract group (10 or 100 mg/kg) compared to the OVA group. Serum levels of Th1 (TNF-α) and Th2 (IL-4, IL-5, and IL-6) cytokines and IgE levels (both total and OVA-specific) were significantly reduced by administration of ethanol extract of TQ at 100 mg/kg. The thicknesses of the nasal septum and epithelium were significantly reduced by the administration of ethanol extract of TQ. These results suggest that TQ may inhibit early and late phases of AR reactions.

Long-term hypoxic hUCMSCs-derived extracellular vesicles alleviates allergic rhinitis through triggering immunotolerance of their VEGF-mediated inhibition of dendritic cells maturation

BackgroundExtensions of mesenchymal stem cells (MSCs) in vitro may lead to the loss of their biological functions. However, hypoxic culturation has been shown to enhance the proliferation, survival, and immunomodulatory capacity of MSCs. ObjectiveWe aimed to investigate the effects of long-term hypoxic cultivation on the properties of human umbilical cord-derived MSCs (hUCMSCs) and the therapeutic effects of their extracellular vesicles (EVs) in allergic rhinitis (AR). MethodsProliferation, senescence, telomerase activity and multipotent properties of hUCMSCs were analyzed under long-term culturation of hypoxia (1%) or normoxia (21%), and the therapeutic effects of their conditional medium (CM) and EVs were evaluated in OVA-induced AR mice. Effects of hypoxia-EVs (Hy-EVs) or normoxia-EVs (No-EVs) on human monocyte-derived dendritic cells (DCs) were investigated, and the possible mechanisms of Hy-EVs in induction of immunotolerance were further explored. ResultsLong-term hypoxia significantly promoted the proliferation, inhibited cell senescence, maintained the multipotent status of hUCMSCs. Hy-CM and Hy-EVs showed better therapeutic effects in AR mice compared to No-EVs, seen as improvement of AR-related behaviors such as rubbing and sneezing, and attenuation of inflammation in nasal tissues. In addition, Hy-EVs significantly reduced the expressions of HLA-DR, CD80, CD40, and CD83 induced by OVA plus LPS in DCs, inhibiting the maturation of DCs. Furthermore, we observed that VEGF was remarkably enriched in Hy-EVs, but not in No-EVs, and the inhibition of DCs maturation was markedly neutralized by VEGF antibodies, suggesting that VEGF derived from Hy-EVs was responsible for the inhibition of DCs maturation. ConclusionOur results demonstrated that long-term hypoxia significantly promoted the proliferation, inhibited cell senescence, maintained the multipotent status of hUCMSCs, and hypoxia treated hUCMSCs-derived EVs enhanced their therapeutic effects in AR mice through VEGF-mediated inhibition of DCs maturation.

Saikosaponin D inhibits nasal inflammation by regulating the transcription factors T-box protein expressed in T cells/GATA-3 and retinoic acid-related orphan nuclear receptor γt in a murine model of allergic rhinitis

ContextSaikosaponin D (SSD) is a commonly prescribed agent against inflammatory diseases in Asian countries. However, the anti-allergic inflammatory effect of SSD in allergic rhinitis (AR) model is not well known. ObjectiveWe investigated the anti-allergic and anti-inflammatory effects of SSD on the ovalbumin (OVA)-induced AR model. Materials and methodBALB/c mice were divided into the control, OVA, OVA + SSD, and OVA + dexamethasone (Dex) groups. AR was established by intraperitoneal injection with OVA adsorbed to aluminum hydroxide, and intranasal challenge with OVA. Thereafter, the mice were treated with 10 mg/kg BW (Body weight) of OVA + SSD and 2.5 mg/kg BW of Dex orally for 11 days before being challenged. Subsequently, the mice were challenged with OVA 1 h after SSD or Dex treatment. The Control group was treated with saline only. ResultsThe addition of 10 mg/kg BW of OVA + SSD significantly ameliorated the nasal symptoms including sneezing and rubbing from 30 ± 5.2 times in OVA group to 20 ± 5.8 times. Moreover, OVA + SSD group decreased the production of TNF-α, IL-4, IL-5, IL-17, GATA-3 and RORγ about 1.2–1.4-fold compared to the OVA-induced AR mice near to 2.5 mg/kg BW of Dex levels. Meanwhile OVA + SSD group slightly increased the levels of INF-γ, IL-12 and T-bet about 1.8–2.0-fold compared to the OVA group near to control group. Notably, OVA + SSD group also reduced the levels of OVA-specific IgE and IgG1 about 0.5–2.5-fold compared OVA group but increased the levels of IgG2a in serum. The results were analyzed using Graph Pad Prism software (v5.0, La Jolla, CA, USA). ConclusionSSD may represent an alternative therapeutic approach for the treatment of patients with AR through the regulation of transcription factors T-bet, GATA-3, and RORγ in inflammatory cells.

MiR-29a-3p promotes nasal epithelial barrier dysfunction via direct targeting of CTNNB1-VCL module in allergic rhinitis

Allergic rhinitis (AR) is resulted from immunoglobulin E (IgE)-mediated reactions to inhaled allergens which elicit mucosal inflammation and impair epithelial barrier integrity. However, whether miR-29a-3p as an epigenetic regulator that can contribute to epithelial barrier dysfunction in the pathogenesis of AR, and its underlying mechanism remians unclear. In this study, we discovered that miR-29a-3p was upregulated in AR patients and preferentially expressed in epithelial and glandular cells of nasal mucosa. VCL and CTNNB1, candidate target genes of miR-29a-3p, were predicted with several databases, including miRDB, miRanda, microT-CDS and TargetScan, and were validated through dual-luciferase reporter assay system. These two proteins were strongly associated with adherens junction (AJ) and tight junction (TJ) of nasal mucosa epithelial cells, in which played vital roles in mucosal integrity and nasal epithelial barrier function stability. Results for HNEpC culture and in vitro treatment experiments showed that expression of VCL and CTNNB1 were inhibited by miR-29a-3p mimic and were enhanced by miR-29a-3p inhibitor. In OVA-induced AR mice model, the expression pattern of miR-29a-3p and its target genes (Vcl and Ctnnb1) were consistent with the aforementioned quantitative results in AR patients, and miR-29a-3p antagomir could partially alleviate the symptom of OVA-induced AR in mice, restoring mucosal integrity and paracellular barrier function. In conclusion, our findings indicate that miR-29a-3p targets CTNNB1 and VCL to regulate nasal epithelial permeability and barrier function integrity, which may serve as a potential novel therapeutic target for the treatment of AR.

Therapeutic effects of Pulsatilla koreana Nakai extract on ovalbumin-induced allergic rhinitis by inhibition of Th2 cell activation and differentiation via the IL-4/STAT6/GATA3 pathway

Allergic rhinitis (AR), caused by immunoglobulin E (IgE)-mediated inflammation, generally occurs in the upper respiratory tract. T helper type 2 (Th2) cell-mediated cytokines, including interleukin (IL)-4, IL-5, and IL-13, are important factors in AR pathogenesis. Despite various treatment options, the difficulty in alleviating AR and pharmacological side effects necessitate development of new therapies. The root of Pulsatilla koreana Nakai (P. koreana), a pasque flower, has been used as a herbal medicine. However, its effects on AR remain unclear; therefore, we aimed to explore this subject in the current study. The therapeutic effects of P. koreana water extract (PKN) on the pathophysiological functions of the nasal mucosa was examined in ovalbumin (OVA)-induced AR mice. The effect of PKN on Th2 activation and differentiation was evaluated using concanavalin A-induced splenocytes and differentiated Th2 cells from naïve CD4+ T cells. We also investigated the effect of changes in JAK/STAT6/GATA3 signaling on IL-4-induced Th2 cells. In OVA-induced AR mice, PKN administration alleviated allergic nasal symptoms and decreased the total number of immune cells, lymphocytes, neutrophils, and eosinophils in nasal lavage fluid; serum levels of OVA-specific IgE, histamine, and IL-13 were also significantly reduced. PKN also ameliorated OVA-induced nasal mucosal tissue thickening by inhibiting inflammation and goblet cell hyperplasia. PKN treatment significantly inhibited Th2 activity and differentiation through the IL-4/STAT-6/GATA3 pathway in Th2 cells. PKN is an effective AR treatment with the potential to improve patients' daily lives by regulating the allergic inflammatory response induced by Th2 cells.

Gleditsia sinensis Lam. aqueous extract attenuates nasal inflammation in allergic rhinitis by inhibiting MUC5AC production through suppression of the STAT3/STAT6 pathway

Allergic rhinitis (AR), a chronic respiratory inflammatory disease, is among the most common chronic diseases reported worldwide. Mucus hypersecretion is a critical feature of AR pathogenesis. Although the Gleditsia sinensis extract has several beneficial effects on human health, its effects on allergic inflammation have not yet been investigated. In this study, we examined the effects of G. sinensis aqueous extract (GSAE) on nasal inflammation in an ovalbumin (OVA)-induced AR mouse model. GSAE was administered orally for 1 week and then the clinical nasal symptoms were evaluated. The levels of histamine, OVA-specific immunoglobulin (Ig) E, and interleukin (IL)-13 were measured in the serum using an enzyme-linked immunosorbent assay (ELISA). Inflammatory cells were then counted in the nasal lavage fluid (NALF) and histopathology in the nasal epithelium was evaluated. STAT3/STAT6 phosphorylation was examined in primary human nasal epithelial cells (HNEpCs) using western blot analysis. Oral administration of GSAE to OVA-induced AR mice alleviated nasal clinical symptoms and reduced OVA-specific immunoglobulin E, interleukin (IL)-13, and histamine levels. The accumulation of eosinophils in nasal lavage fluid, nasal mucosa, mast cells, goblet cells, and mucin 5AC (MUC5AC) in the nasal epithelium was also inhibited by GSAE. Treatment with GSAE inhibited the production of MUC5AC in IL-4/IL-13-stimulated primary human nasal epithelial cells through the signal transducer and activator of transcription (STAT)3/STAT6 signaling pathway. These results indicated that GSAE reduces nasal inflammation suggesting that it is a potential treatment option for AR.

Antiallergic Effects of N,N-dicoumaroylspermidine Isolated from Lithospermum erythrorhizon on Mast Cells and Ovalbumin-Induced Allergic Rhinitis.

In East Asia, the dried root of Lithospermum erythrorhizon has been utilized as an anti-inflammatory, antipyretic, detoxifying, and anti-inflammatory agent. Recently, we reported that L. erythrorhizon protects against allergic rhinitis; however, the component within L. erythrorhizon that exerts antiallergic activity remains unknown. The purpose of the current study was to isolate and characterize the antiallergic active components in an ethanolic extract of L. erythrorhizon roots. We examined the antiallergic effects of L. erythrorhizon reflux ethanol extracts in an ovalbumin (OVA)-induced allergic rhinitis mouse model, and compared the chemical compounds extracted using the hot reflux and cold extraction methods. Chromatographic separation identified two novel anthraquinones, erythrin A and B, one newly discovered compound from the Lithospermum genus, N1″,N3″-dicoumaroylspermidine, and nineteen other recognized compounds. Their chemical structures were elucidated by single (1D) and 2D analysis of nuclear magnetic resonance (NMR) spectroscopic data, as well as high resolution mass spectrometry. Among the identified compounds, N,N′-dicoumaroylspermidine strongly inhibited the release of β-hexosaminidase, as well as the production of IL-3, IL-4, and IL-13 by IgE-sensitized and BSA-stimulated RBL-2H3 cells. Using the OVA-induced allergic rhinitis mouse model, we showed that N,N′-dicoumaroylspermidine reduced the production of serum OVA-specific IgE and the number of inflammatory cells in nasal lavage fluid. N,N′-dicoumaroylspermidine isolated from L. erythrorhizon exhibits antiallergic properties, making it potentially effective for allergic rhinitis.

Tanshinone IIA alleviates ovalbumin-induced allergic rhinitis symptoms by inhibiting Th2 cytokine production and mast cell histamine release in mice

Context Studies have shown that tanshinone IIA (TIIA) has an anti-inflammatory effect, but the effect on allergic rhinitis (AR) is unclear. Objective In this study, we explore the effect of TIIA on AR. Materials and methods AR mice model was established by the intraperitoneal (ip) injection of 50 μg ovalbumin (OVA). AR mice in the dose tested groups were treated with TIIA (10 mg/kg/d, ip) or dexamethasone (Dex) (2.5 mg/kg/d, oral). The number of nasal rubbing in mice was counted. Inflammatory, goblet and mast cells in nasal mucosal tissue were detected. The contents of histamine, OVA-immunoglobulin E (IgE), OVA-immunoglobulin G1 (IgG1), tumour necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-5, interferon-γ (IFN-γ) and IL-12 in nasal lavage fluid (NALF) or serum were measured. Human mast cells (HMC-1) were treated with C48/80 to release histamine or TIIA for therapeutic effect, and the cell viability, histamine content and mast cell degranulation were examined. Results OVA promoted the number of nasal rubbings in mice (78 times/10 min, p< 0.001), increased the inflammatory, goblet and mast cells in nasal mucosal tissue, and significantly (p< 0.001) elevated the levels of histamine (120 ng/mL), OVA-IgE (2 pg/mL), OVA-IgG1 (90 ng/mL), TNF-α (2.3 pg/mL), IL-4 (150 pg/mL) and IL-5 (65 pg/mL) in serum or NALF of OVA-induced AR mice. However, both TIIA and Dex inhibited the effect of OVA on AR mice. Besides, TIIA reversed the promotion of histamine release (30%) and mast cell degranulation induced by C48/80. Discussion and conclusions TIIA alleviates OVA-induced AR symptoms in AR mice, and may be applied as a therapeutic drug for patients with Th2-, or mast cell-allergic disorders.

RETRACTED ARTICLE: Ponicidin treatment attenuates ovalbumin-induced allergic rhinitis in mice and RBL-2H3 cell line models

Allergic rhinitis (AR) is the chronic type of rhinitis that arises due to hypersensitivity response. It is caused by nasal mucosa inflammation and becomes a social burden in later stages. Ponicidin is a diterpenoid that is isolated from herbs like Rabdosia rubescens and possesses anti-inflammatory properties. Hence, the present study was designed to analyze the effects of Ponicidin against AR using ovalbumin (OVA)-sensitized murine model and also to reveal the mode of action of Ponicidin. Mice were sensitized with 75 μg of OVA with 2 mg of aluminium hydroxide in 200 μl of buffer for 0, 7, 14, 21 days to provoke the AR. Ponicidin treatment was given in the diet at different doses (5, 10, 15 mg/kg). The nose-rubbing numbers were noted carefully. The levels of histamine, inflammatory cytokines, and NF‐κB DNA binding assay were assessed by the assay kits. The inflammatory cell counts were performed using hemocytometer. The lung tissues were analysed microscopically to identify the histological changes. The viability of control and treated RBL-2H3 cells were analyzed by MTT assay. The β-hexosaminidase activity was assayed using kit. Results showed that Ponicidin significantly attenuated nasal rubbing in OVA-induced AR mice by suppressing histamine release, inflammatory cell numbers and secretion of inflammatory cytokines. The effect of the Ponicidin was comparable to that of the standard drug dexamethasone. In RBL-2H3 cells also, Ponicidin decreased secretion of histamine and inflammatory cytokines. Thus, it can be inferred that Ponicidin can emerge as an effective drug in the management of AR.

The Immuno-Modulatory Activities of Pentaherbs Formula on Ovalbumin-Induced Allergic Rhinitis Mice via the Activation of Th1 and Treg Cells and Inhibition of Th2 and Th17 Cells.

Allergic rhinitis (AR) is a highly prevalent allergic disease induced by immunoglobulin (Ig) E-mediated hypersensitivity reaction at the nasal epithelium against inhaled allergens. Previous studies have demonstrated that Pentaherbs formula (PHF), a modified herbal formula comprising five herbal medicines (Flos Lonicerae, Herba Menthae, Cortex Phellodendri, Cortex Moutan and Rhizoma Atractylodis), could suppress various immune effector cells to exert anti-inflammatory and anti-allergic effects in allergic asthma and atopic dermatitis. The present study aimed to further determine the anti-inflammatory activities of PHF in an ovalbumin (OVA)-induced AR BALB/c mouse model. Nasal symptoms such as sneezing and nose rubbing were recorded and the serum total IgE and OVA-specific IgG1, as well as interleukin (IL)-4, IL-5, IL-10, IL-13, chemokines CXCL9 CXCL10, and tumor necrosis factor (TNF)-α concentrations in nasal lavage fluid (NALF) were measured during different treatments. Effects of PHF on the expression of inflammatory mediators in the sinonasal mucosa were quantified using real-time QPCR. PHF was found to suppress allergic symptoms, infiltration of inflammatory cells, and hyperplasia of goblet cells in the nasal epithelium of the OVA-induced AR mice. PHF could reduce OVA-specific IgG1 level in serum, and TNF-α and IL-10 in nasal lavage fluid (NALF), significantly up-regulate the splenic regulatory T (Treg) cell level, increase the Type 1 helper T cell (Th1)/Type 2 helper T cell (Th2) ratio, and reduce the Th17 cells (all p < 0.05). PHF could also alleviate in situ inflammation in sinonasal mucosa of OVA-induced AR mice. In conclusion, oral treatment of PHF showed immuno-modulatory activities in the OVA-induced AR mice by regulating the splenic T cell population to suppress the nasal allergy symptoms and modulating inflammatory mediators, implicating that PHF could be a therapeutic strategy for allergic rhinitis.

D-Pinitol Attenuated Ovalbumin-induced Allergic Rhinitis in Experimental Mice via Balancing Th1/Th2 Response.

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.

PM2.5 Exacerbates Oxidative Stress and Inflammatory Response through the Nrf2/NF-κB Signaling Pathway in OVA-Induced Allergic Rhinitis Mouse Model.

Air pollution-related particulate matter (PM) exposure reportedly enhances allergic airway inflammation. Some studies have shown an association between PM exposure and a risk for allergic rhinitis (AR). However, the effect of PM for AR is not fully understood. An AR mouse model was developed by intranasal administration of 100 μg/mouse PM with a less than or equal to 2.5 μm in aerodynamic diameter (PM2.5) solution, and then by intraperitoneal injection of ovalbumin (OVA) with alum and intranasal challenging with 10 mg/mL OVA. The effects of PM2.5 on oxidative stress and inflammatory response via the Nrf2/NF-κB signaling pathway in mice with or without AR indicating by histological, serum, and protein analyses were examined. PM2.5 administration enhanced allergic inflammatory cell expression in the nasal mucosa through increasing the expression of inflammatory cytokine and reducing the release of Treg cytokine in OVA-induced AR mice, although PM2.5 exposure itself induced neither allergic responses nor damage to nasal and lung tissues. Notably, repeated OVA-immunization markedly impaired the nasal mucosa in the septum region. Moreover, AR with PM2.5 exposure reinforced this impairment in OVA-induced AR mice. Long-term PM2.5 exposure strengthened allergic reactions by inducing the oxidative through malondialdehyde production. The present study also provided evidence, for the first time, that activity of the Nrf2 signaling pathway is inhibited in PM2.5 exposed AR mice. Furthermore, PM2.5 exposure increased the histopathological changes of nasal and lung tissues and related the inflammatory cytokine, and clearly enhanced PM2.5 phagocytosis by alveolar macrophages via activating the NF-κB signaling pathway. These obtained results suggest that AR patients may experience exacerbation of allergic responses in areas with prolonged PM2.5 exposure.

Anti-allergic effects of Asarum heterotropoides on an ovalbumin-induced allergic rhinitis murine model

Allergic rhinitis (AR) is a common chronic respiratory disease. Asarum heterotropoides (AH) is predicted to be a treatment for allergic diseases, but its therapeutic effect is unclear. We aimed to determine the anti-allergic effects of AH in mice with ovalbumin (OVA)-induced AR. OVA-induced AR mouse model was constructed, and AH was orally administered for a week; next, nasal clinical symptoms were evaluated. The levels of serum histamine, OVA-specific IgE, and IL-13 were measured by ELISA. Inflammatory cells, including leukocytes, neutrophils, eosinophils, and macrophages were counted in the nasal lavage fluid (NALF). Histopathological examinations of the nasal tissues were performed using H&E, Giemsa, and PAS staining. The production of periostin and eotaxin-3 from AH-treated human nasal epithelial cells (HNEpCs) in vitro, was measured using ELISA. Oral administration of AH alleviated allergic symptoms in mice with AR; significantly decreased levels of allergic mediators, such as serum histamine and OVA-specific IgE. The decrease in allergic symptoms positively correlated with the decrease in serum allergic mediators. The NALF of AH-treated AR mice demonstrated lower number of eosinophils. AH demonstrated a capacity to reduce the infiltration of mast cells, eosinophils, and goblet cells, thereby resulting in thinner nasal tissues. Moreover, treatment of HNEpCs with AH demonstrated suppressed production of periostin and eotaxin-3. AH exerts a therapeutic effect in modulating AR through multi-target and multi-function influence on regulating B cells, mast cells, eosinophils, goblet cells, and epithelial cells.

RETRACTED ARTICLE: MicroRNA-29 mediates anti-inflammatory effects and alleviation of allergic responses and symptoms in mice with allergic rhinitis

BackgroundTo investigate the role of microRNA-29 (miR-29) in mice with allergic rhinitis (AR) and its underlying mechanism.MethodsAR 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.ResultsDecreased 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.ConclusionMiR-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.