Murine Model Of Allergic Rhinitis Research Articles

Anti-allergic effects of the probiotic preparations of enterococcus on experimental allergic rhinitis in mice

The aim of this study was to investigate the anti-allergic effects of lysozyme/heat-treated Enterococcus faecalis FK-23 (LFK) and heat-treated Enterococcus faecium sp. TN-3 (TN) on experimental allergic rhinitis (AR). A total of twenty-four BALB/c mice were divided into four groups randomly: (1) positive control group, (2) LFK-fed group, (3) TN-fed group, and (4) negative control group. To establish the murine AR model, intraperitoneal injection and nasal drip with ovalbumin (OVA) were performed. Saline was used instead of OVA for negative control. Probiotic preparations of LFK and TN were orally administrated for 42 days [60 mg (0.5 ml)/d] in LFK-fed and TN-fed mice, respectively. The positive and negative control mice received saline orally for 42 days. Nasal rubbing and sneezing were monitored on d 21, d 27, and d 35. After the final challenge, mice were sacrificed on d 42, and eosinophilic infiltration into the nasal mucosa was quantified (H&E stain). IFN-gamma, IL4 and OVA-specific IgE levels in the sera and splenocyte culture supernatants were determined by ELISA kits. Nasal rubbing of LFK-fed mice was significantly reduced compared to the positive control group on day 27 (t = 2.95, P = 0.028). Both in the LFK-fed and TN-fed mice, nasal rubbing (t value was 3.75 and 3.06, P value was 0.005 and 0.011, respectively) and sneezing (t value was 2.56 and 3.35, P value was 0.038 and 0. 01, respectively) were significantly decreased compared to the positive control group on d 35. The H&E strain section of nasal tissue showed that eosinophil influx into the nasal mucosa decreased significantly both in the LFK-fed and TN-fed mice compared to the positive control group on day 42 (t value was 3.44 and 2.97, P value was 0.014 and 0.025, respectively); however, the LFK-fed mice and TN-fed mice had significant eosinophil influx into the nasal mucosa than that in the negative control group (t value was 2.54 and 3.39, P value was 0.044 and 0.015, respectively). There were no significant differences in the serum levels of IL-4 and OVA-specific IgE, as well as the levels of IFN-gamma and IL-4 in splenocyte culture supernatants between the LFK-fed group and positive control group on d 42 (all P > 0.05). Interestingly, the TN-fed mice had significantly higher serum levels of IFN-gamma compared to the LFK-fed mice [TN-fed mice: (27.07 +/- 3.83) pg/ml, LFK-fed mice: (14.83 +/- 0.99) pg/ml; Z = 2.49, P = 0.016], but not the negative control group [negative control group: (37.12 +/- 1.65) pg/ml; Z = 1.18, P = 0.343] on day 42. The serum levels of IL-4 were significantly lower in the TN-fed mice than those in the positive control group [TN-fed mice: (34.48 +/- 7.53) pg/ml, positive control group: (58.68 +/- 6.59) pg/ml; Z = 2.11, P = 0.035]; however, the levels were significantly higher in the TN-fed mice than those in the negative control group [negative control group: (20.22 +/- 1.75) pg/ml; Z = 2. 31, P = 0.021]. The TN-fed mice had significantly higher levels of IFN-gamma in splenocyte culture supernatants compared to the LFK-fed mice (Z = 2.72, P = 0.03) and the positive control group (Z = 2.30, P = 0.029), whilst the splenocyte culture supernatant levels of IL-4 (Z = 2.12, P = 0.034) and the serum levels of OVA-specific IgE (Z = 2.31, P = 0.021) were significantly lower in the TN-fed mice compared to the positive control mice. It is suggested that oral administration of probiotic LFK or TN may alleviate nasal symptoms and reduce nasal eosinophilia in the murine AR model. TN supplementation has obviously regulatory effects on the cytokine levels of IFN-gamma and IL-4, and significantly inhibitory effects on antigen-specific IgE levels.

Antiallergic Effect of Anti–Siglec-F through Reduction of Eosinophilic Inflammation in Murine Allergic Rhinitis

Sialic acid-binding Ig-like lectin-F (Siglec-F) in mice and its functional paralog Siglec-8 in humans are transmembrane receptors that play a role in the apoptosis of eosinophils. We aimed to evaluate the therapeutic potential of anti-Siglec-F antibodies in a murine model of allergic rhinitis. Twenty-eight BALB/c mice were used. In group A (control group, n = 7), mice were sensitized and challenged with saline. In group B (ovalbumin [OVA] challenge group, n = 7), OVA was used for i.p. sensitization and intranasal challenge. Mice in group C (control IgG group, n = 7) or those in group D (anti-Siglec-F group, n = 7) had been given rabbit control IgG or anti-Siglec-F antibody injections, respectively. We assessed the number of nose-scratching events; serum total/OVA-specific IgE; the number of eosinophils, neutrophils, and lymphocytes in bronchoalveolar lavage (BAL) fluid; histopathological changes in nasal cavity tissues; and the levels of IL-4, IL-5, and IL-13 in BAL fluid. Mice in group D had significantly less nose scratching. Serum total and OVA-specific IgE were not significantly changed. The number of eosinophils in BAL fluid and in the lamina propria of the nasal cavity mucosa was significantly decreased with anti-Siglec-F antibody treatment. The levels of Th2 cytokines such as IL-4, IL-5, and IL-13 were also significantly decreased with anti-Siglec-F antibody treatment. Anti-Siglec-F antibody has beneficial effects in a mouse model of experimental allergic rhinitis.

The effect of Korean red ginseng on allergic inflammation in a murine model of allergic rhinitis

Korean red ginseng (KRG) is reported to have anti-allergic properties, including beneficial effects on asthma and atopic dermatitis. However, its effect on allergic rhinitis has not been studied extensively. This study examined how KRG affected allergic inflammation of the nasal cavity in an allergic mouse model. A total of 40 Balb/c female mice were divided into four experimental groups according to treatment and allergic state: group 1 (G1), saline only; group 2 (G2), ovalbumin (OVA); group 3 (G3), OVA+KRG; and group 4 (G4), OVA+dexamethasone. Serum IgE levels were significantly lower in the KRG treatment group (G3) than in the allergic group (G2). However, serum IgG1 levels did not differ between G2 and G3. In the nasal lavage fluid, IL-4 and IL-5 levels were significantly lower in G3 than in G2 (p<0.05). H&E and Luna staining revealed that the eosinophil count was lower in G3 and G4 than in G2 (p<0.05). Immunohistochemical staining revealed that there were fewer IL-4-, IL- 5-, and MUC5AC-positive cells in G3 and G4 than in G2 (p<0.05). These results indicate that KRG reduces the nasal allergic inflammatory reaction in an allergic murine model by reducing Th2 cytokines.

Extra domain-A fibronectin is necessary for the development of nasal remodeling in chronic allergen-induced rhinitis

BackgroundExtra domain A–containing fibronectin (EDA-FN) is necessary for the development of allergen-induced lower airway fibrosis. The pathogenesis of fibrosis in allergic rhinitis has not been well studied. ObjectivesTo determine whether EDA-fibronectin is necessary for the development of nasal remodeling in a murine model of chronic allergic rhinitis and in human allergic rhinitis. MethodsEDA(-/-) and wild-type (WT) C57Bl/6 mice were sensitized intraperitoneally and then challenged with inhaled ovalbumin (OVA) or saline for 2 and 5 weeks. Clinical signs of rhinitis and histological analysis of nasal tissue were evaluated. Immunohistological staining for EDA-FN was performed in human tissue of inferior nasal conchae from patients with allergic rhinitis and controls. ResultsAfter 2 weeks of allergen exposure, only goblet cell hyperplasia and perivascular eosinophilia were observed. After 5 weeks, goblet cell number, thickening of the subepithelial layer, and extent and area of collagen deposition were increased in the nasal tissue of WT OVA (ovalbumin)-challenged mice as compared with saline controls (P < .0001, P < .0001, P = .018, and P = .03, respectively). Clinical signs of rhinitis were observed only in WT OVA-challenged mice. In the EDA(-/-) mice exposed to OVA, collagen deposition, collagen area, and subepithelial thickness showed no increase and were similar to saline control mice, whereas goblet cell hyperplasia was similar to WT OVA-challenged mice. EDA-FN expression was prominent in inferior conchae from patients with allergic rhinitis but was absent in control patients. ConclusionEDA-containing fibronectin is necessary for the development of nasal tissue fibrotic remodeling process in both murine and human allergic rhinitis.

Comparison of antiallergic effects of pneumococcal conjugate vaccine and pneumococcal polysaccharide vaccine in a murine model of allergic rhinitis

Pneumococcal vaccines have been widely used, and Streptococcus pneumoniae has been suggested to be an effective therapeutic agent in allergic disease. The present study was performed to evaluate the effects of pneumococcal polysaccharide vaccine (PV) and pneumococcal protein conjugate vaccine (PCV), and to examine differences between the vaccines in a murine model of allergic rhinitis. In vivo study using an animal model. Catholic Research Institutes of Medical Science. Allergic rhinitis was induced in 40 BALB/c mice by intraperitoneal sensitization and intranasal challenge with Dermatophagoides farinae (Derf). The animals were divided into four groups: control, Derf, PV, and PCV. Interferon-γ, interleukin-13, and interleukin-10 levels in nasal lavage fluid and Derf-specific immunoglobulin E levels in serum were measured. The levels of T-bet, GATA-3, and Foxp3 mRNA expression in splenic mononuclear cells were determined. The number of CD4(+) CD25(+) Foxp3(+) regulatory T cells in splenic mononuclear cells was compared between groups by flow cytometry. Allergic symptom scores, T-bet and GATA-3 mRNA levels, serum Derf-specific immunoglobulin E levels, and tissue eosinophil counts were lower in the PV and PCV groups than the Derf group (P < 0.05). The regulatory T (Treg) cell indicators, Foxp3 mRNA, and percentages of CD4(+) CD25(+) Foxp3(+) T cells were increased in the PV and PCV groups (P < 0.05). Both PV and PCV suppressed the allergen-specific T helper 2 response and induced regulatory T cells in a murine model of allergic rhinitis. However, PV and PCV may activate Treg cells via different mechanisms. N/A.

In vivo intranasal anti-CD23 treatment inhibits allergic responses in a murine model of allergic rhinitis

Although CD23-dependent transcytosis of IgE and IgE-derived immune complexes across respiratory epithelial cells is likely to play a pivotal role in the initiation and development of airway allergic inflammation, there is currently a lack of physiological support for this phenomena to suggest that the targeting of CD23 could be used as a means of therapeutic intervention. The present study was designed to detect the CD23 expression in the nasal mucosa of allergic rhinitis (AR) murine model by immunohistochemistry and western blotting, and to investigate whether intranasal anti-CD23 treatment could inhibit allergen-induced upper airway inflammation in the AR model. This is the first report to show that CD23 was constitutively expressed in murine nasal epithelial cells, and its expression was significantly up-regulated in the AR murine model. In vivo, the up-regulation of CD23 expression was correlated with increased serum IL-4 levels. Following intranasal anti-CD23 treatment, nasal symptoms were alleviated and histopathologic examination showed a significant decrease in eosinophilic infiltration. Meanwhile, ELISA analysis showed levels of serum leukotriene C4 (LTC4), eosinophil cation protein (ECP), ovalbumin (OVA)-specific IgE and IL-4 also significantly decreased, as were LTC4 and OVA-specific IgE in the nasal lavage fluid. Furthermore, Western blotting analysis showed that ECP expression in the nasal mucosa was down-regulated. Finally, flow cytometric analysis revealed anti-CD23 treatment inhibited Th2 cell responses. These results indicate that intranasal anti-CD23 treatment can reduce allergic responses in a murine model of allergic rhinitis.

Allied health – 3008. Comparison of anti-allergic effect of pneumococcal conjugated vaccine and pneumococcal polysaccharide vaccine in a murine model of house dust mite allergic rhinitis

The T-bet m RNA level was lower in the PV and PCV group than Der f group (p< 0.05). The IL-13, GATA-3 mRNA level and serum Der f-specific IgE and eosinophil were lower in the PV and PCV group than Der f group (p< 0.05). Foxp3 mRNA expression in the PV and PCV group was elevated compared to the Der f group (p < 0.05). In flow cytometry, the PV group (p < 0.05) and the PCV group (p < 0.05) had higher percentages of CD4+ CD25+Foxp3+ T cells than the Der f group. In the PV group, the percentage of these cells was higher than that in the PCV group. (p=0.00). Conclusions These results suggest that the pneumococcal polysaccharide vaccines will suppress the allergen-specific Th2 response and enhanced the induction of regulatory T cells in a model of allergic rhinitis. And the process to work regulatory T cell can be different between the PV and PCV group.

HIF-1α inhibition reduces nasal inflammation in a murine allergic rhinitis model.

BackgroundHypoxia-inducible factor 1α (HIF-1α) is an important regulator of immune and inflammatory responses. We hypothesized that nasal allergic inflammation is attenuated by HIF-1α inhibition and strengthened by HIF-1α stabilization.ObjectiveTo elucidate the role of HIF-1α in a murine model of allergic rhinitis (AR).MethodsMice were pretreated with the HIF-1α inhibitor 2-methoxyestradiol (2ME2) or the HIF-1α inducer cobalt chloride (CoCl2) in an established AR murine model using ovalbumin (OVA)-sensitized BALB/c mice. HIF-1α and vascular endothelial growth factor (VEGF) expression in nasal mucosa was measured and multiple parameters of allergic responses were evaluated.ResultsHIF-1α and VEGF levels were locally up-regulated in nasal mucosa during AR. Inflammatory responses to OVA challenge, including nasal symptoms, inflammatory cell infiltration, eosinophil recruitment, up-regulation of T-helper type 2 cytokines in nasal lavage fluid, and serum OVA-specific IgE levels were present in the OVA-challenged mice. 2ME2 effectively inhibited HIF-1α and VEGF expression and attenuated the inflammatory responses. Stabilization of HIF-1α by CoCl2 facilitated nasal allergic inflammation. HIF-1α protein levels in nasal airways correlated with the severity of AR in mice.ConclusionsHIF-1α is intimately involved in the pathogenesis of nasal allergies, and the inhibition of HIF-1α may be useful as a novel therapeutic approach for AR.

Sublingual Immunotherapy Induces Regulatory Function of IL-10-Expressing CD4+CD25+Foxp3+T Cells of Cervical Lymph Nodes in Murine Allergic Rhinitis Model

Sublingual immunotherapy (SLIT) has been considered to be a painless and efficacious therapeutic treatment of allergic rhinitis which is known as type I allergy of nasal mucosa. Nevertheless, its mechanisms need to be further investigated. In this study, we constructed an effective murine model of sublingual immunotherapy in allergic rhinitis, in which mice were sublingually administered with ovalbumin (OVA) followed by intraperitoneal sensitization and nasal challenge of OVA. Sublingually treated mice showed significantly decreased specific IgE responses as well as suppressed Th2 immune responses. Sublingual administration of OVA did not alter the frequency of CD4+CD25+ regulatory T cells (Tregs), but led to upregulation of Foxp3- and IL-10-specific mRNAs in the Tregs of cervical lymph nodes (CLN), which strongly suppressed Th2 cytokine production from CD4+CD25− effector T cells in vitro. Furthermore, sublingual administration of plasmids encoding the lymphoid chemokines CCL19 and CCL21-Ser DNA together with OVA suppressed allergic responses. These results suggest that IL-10-expressing CD4+CD25+Foxp3+ Tregs in CLN are involved in the suppression of allergic responses and that CCL19/CCL21 may contribute to it in mice that received SLIT.

Blocking interleukin-17 attenuates enhanced inflammation by staphylococcal enterotoxin B in murine allergic rhinitis model

Conclusion: The results of this study suggest that staphylococcal enterotoxin B (SEB) enhances inflammation in allergic rhinitis (AR) and interleukin (IL)-17 may play a significant role in regulation of the inflammatory process induced by SEB. Objectives: Exposure to SEB is associated with severe symptoms in AR patients. However, how SEB influences the inflammatory process in AR has not been elucidated so far. The aim of this study was to identify the role of SEB and IL-17 in AR. Methods: BALB/c and IL-17-deficient mice were divided into three groups: control, OVA, and SEB groups. The control group was challenged with phosphate-buffered saline, the AR group was challenged with ovalbumin (OVA), and the SEB group was treated with SEB before OVA challenge. Nasal symptoms, eosinophil infiltration, serum total and OVA-specific immunoglobulin E levels, and cytokine levels including IL-1β, IL-4, IL-6, and interferon (IFN)-γ in splenocyte culture were compared between the groups. Results: The SEB group produced significantly greater amounts of cytokines such as IL-1β, IL-4, IL-6, and IFN-γ than the OVA group in wild-type mice. However, these enhanced inflammatory responses in the SEB group compared with the OVA group were not observed in IL-17-deficient mice.

A critical role of IL-33 in experimental allergic rhinitis

We reported previously that serum levels of IL-33 are significantly increased in patients with allergic rhinitis (AR). However, very little is known about the role of IL-33 for the development of AR. We thought to develop a novel murine model of ragweed pollen-specific AR and examined the pathologic role for ragweed-induced IL-33 in the development of AR manifestation using IL-33-deficient (il33(-/-)) mice. Ragweed-immunized and ragweed-challenged mice were examined for early- and late-phase nasal responses. IL-33 protein expression in the nasal epithelial cells of the AR murine model and patients with AR were assessed by using confocal microscopy. After nasal challenge with ragweed pollen, ragweed-immunized wild-type mice manifested early-phase (sneezing) and late-phase (eosinophilic and basophilic accumulation) responses. In contrast, il33(-/-) and FcεRI(-/-) mice did not have both early- and late-phase AR responses. IL-33 protein was constitutively expressed in the nucleus of nasal epithelial cells and was promptly released into nasal fluids in response to nasal exposure to ragweed pollen. In human subjects we revealed constitutive expression of IL-33 protein in the nasal epithelial cells of healthy control subjects and downregulated expression of IL-33 protein in inflamed nasal epithelial cells of patients with AR. IL-33-stimulated mast cells and basophils contributed to the early- and late-phase AR manifestation through increasing histamine release and production of chemoattractants for eosinophils/basophils, respectively. Ragweed pollen-driven endogenous IL-33 contributed to the development of AR responses. IL-33 might present an important therapeutic target for the prevention of AR.

Contribution of interleukin 17A to the development and regulation of allergic inflammation in a murine allergic rhinitis model

BackgroundInterleukin (IL) 17A, a key cytokine of TH17 cells, is a well-known proinflammatory cytokine. Despite the important role of TH17 cells in acute airway inflammation, the role of IL-17A in allergic rhinitis (AR) remains unclear. ObjectiveTo investigate the role of IL-17A in the allergic response in AR. MethodsWild-type BALB/c and IL-17A–deficient mice were immunized intraperitoneally and were challenged intranasally with ovalbumin. Allergic symptom scores, eosinophil infiltration, serum IgE level, and the levels of several cytokines in nasal lavage fluid and splenocyte supernatants were analyzed. ResultsIL-17A levels increased significantly more in ovalbumin-sensitized wild-type mice than in the negative control group. IL-17A–deficient mice showed a significant decrease in allergic symptoms, serum IgE levels, and eosinophil infiltration into the nasal mucosa compared with wild-type mice. IL-17A–deficient mice also showed decreased histamine and cysteinyl leukotriene release. Bone marrow–derived mast cells from IL-17A–deficient mice showed significantly lower degranulation and secretion of tumor necrosis factor α. Moreover, IL-17A deficiency attenuated the IL-5 level in nasal lavage fluid and its production in response to ovalbumin but did not increase interferon γ production and its level in nasal lavage fluid. In addition, secretion of IL-17A from spleen cells induced the expression of proinflammatory cytokine messenger RNA in macrophages. The mean level of proinflammatory cytokines, including tumor necrosis factor α and IL-17, decreased in IL-17A–deficient mice. ConclusionThese results suggest that IL-17A may partly contribute to the development of nasal allergic inflammation in an AR animal model and regulate AR via the activation of proinflammatory cytokines and modulation of TH2 cytokine.

Roles of Periostin in Symptom Manifestation and Airway Remodeling in a Murine Model of Allergic Rhinitis

PurposePeriostin was originally identified as a secreted factor during screening of a mouse osteoblastic library. In a recent study, periostin was found to directly regulate eosinophil accumulation in allergic mucosal inflammation. Chronic eosinophilic inflammation is related to the development of remodeling. The present study examined the expression of periostin and evaluated its role in the inflammatory process and remodeling associated with allergic rhinitis.MethodsA murine model of allergic rhinitis was established in periostin knockout mice. We analyzed the expression of periostin, manifestation of nasal symptoms, eosinophilic inflammation, and subepithelial fibrosis as well as the expression of MMP-2, TIMP-1, and type 1 collagen in nasal tissue.ResultsPeriostin was mainly distributed in the subepithelial tissue of the nasal mucosa. The subepithelial tissue was thinner in the knockout group than in the control group. No differences in the expression of MMP-2 or TIMP-1 were found in the knockout group. However, after a month of allergen challenge, type I collagen in the nasal tissue was lower in the knockout group than in the control group. The number of eosinophils and the symptom score were also lower in the knockout group.ConclusionsPeriostin is expressed in nasal tissues of murine models of allergic rhinitis. Periostin deficiency may affect the remodeling of nasal tissue with reduced subepithelial fibrosis, and lead to less eosinophilic inflammation.

Effects of lysed Enterococcus faecalis FK-23 on experimental allergic rhinitis in a murine model

In the current study, we sought to investigate whether lysed Enterococcus faecalis FK-23 (LFK), a heat-killed probiotic preparation, attenuated eosinophil influx into the upper airway and had immunomodulatory activity in a murine allergic rhinitis model. Eighteen BALB/c mice were divided into three groups; the ovalbumin (OVA)-sensitized/challenged group, which received saline orally for 6 weeks (OVA group), the OVA-sensitized/challenged group, which received LFK orally for 6 weeks (LFK-fed group), and the non-sensitized group, which received saline for 6 weeks (saline control group). Nasal rubbing and sneezing were monitored during the study. After the final challenge, interleukin (IL)-4, interferon (IFN)-γ, and OVA-specific IgE levels in the sera and splenocyte culture supernatants were determined, eosinophilic infiltrate into the upper airway was quantified, and splenic CD4+CD25+ regulatory T cells (Tregs) were examined by flow cytometry. We found that nasal rubbing was significantly reduced in LFK-fed mice compared to the OVA group on d 27 and 35, and sneezing was significantly inhibited by LFK administration for 35 d. LFK-fed mice had significantly less eosinophil influx into the nasal mucosa than the OVA group. There were no significant differences between the LFK-fed group and OVA group in the serum and splenocyte culture supernatant levels of IL-4, IFN-γ, and OVA-specific IgE. Interestingly, the LFK-fed mice had a significantly greater percentage of splenic CD4+CD25+ Tregs than OVA group. Our results indicate that oral administration of LFK may alleviate nasal symptoms, reduce nasal eosinophilia, and increase the percentage of CD4+CD25+ Tregs in experimental allergic rhinitis.

Downregulation of Orai1 expression in the airway alleviates murine allergic rhinitis

Orai1 is the key subunit of the Ca2+-release-activated Ca2+ channel. Our previous report has demonstrated that Orai1 expression in the airway was upregulated in the ovalbumin (OVA)-induced allergic rhinitis (AR) mouse models. To observe whether inhibition of Orai1 expression in the airway could suppress symptoms in a murine model of AR and to assess the impacts of this inhibition on the responses of local and systemic immunocytes, we administered recombinant lentivirus vectors that encoded shRNA against ORAI1 (lenti-ORAI1) into the nostrils of OVA-sensitized mice before the challenges, and analyzed its effect on allergic responses, as compared with the unsensitized mice and untreated AR mice. Administration of lenti-ORAI1 into the nasal cavity successfully infected cells in the epithelial layer of the nasal mucosa, and significantly decreased the frequencies of sneezing and nasal rubbing of the mice. Protein levels of leukotriene C4, OVA-specific IgE, and IL-4 in the nasal lavage fluid and serum and eosinophil cation protein in the serum were also significantly reduced by lenti-ORAI1, as were the mRNA levels of these factors in the nasal mucosa and spleen. These data suggested that administration of lenti-ORAI1 into the nasal cavity effectively decreased Orai1 expression in the nasal mucosa, alleviated AR symptoms, and partially inhibited the hyperresponsiveness of the local and systemic immune cells including T cells, B cells, mast cells and eosinophils that are involved in the pathogenesis of AR.

Anti‐IL‐33 antibody has a therapeutic effect in a murine model of allergic rhinitis

Interleukin (IL)-33 is involved in the Th2 immune response and could play an essential role in nasal allergy. Therefore, we aimed to investigate the therapeutic potential of anti-IL-33 for allergic rhinitis (AR). Twenty-four BALB/c mice were used. In group A (control group, n = 6), mice were sensitized and challenged with saline. Group B [ovalbumin (OVA) group, n = 6] mice received intraperitoneal and intranasal OVA challenge. In group C (control IgG group, n = 6), mice were injected intraperitoneally with rabbit control IgG before OVA challenge. In group D (anti-IL-33 group, n = 6), anti-IL-33 was injected before challenge. We evaluated the number of nose-scratching events and external morphology; serum total and OVA-specific IgE; number of eosinophils, neutrophils, and lymphocytes in bronchoalveolar lavage (BAL) fluid; histopathologic examination of nasal cavity; and IL-4, IL-5, and IL-13 in BAL fluid. Anti-IL-33 treatment significantly reduced the nose-scratching events and ameliorated skin denudation. Serum total and OVA-specific IgE was significantly decreased in group D. The number of eosinophils in BAL fluid was also significantly decreased. Eosinophilic infiltration in the nasal cavity was significantly decreased in group D. IL-4, IL-5, and IL-13 in BAL fluid were also significantly decreased after treatment. Anti-IL-33 antibody has a therapeutic potential for experimental AR.

Role of Angiogenic Factors in Airway Remodeling in an Allergic Rhinitis Murine Model

PurposeThere is growing evidence that nasal airway remodeling occurs in allergic rhinitis (AR). Although angiogenesis is an important component of airway remodeling in asthma, its involvement in AR has been little studied. Furthermore, information regarding the role of potent angiogenic factors, such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), in the nasal airway remodeling process is limited. This study was conducted to investigate the role of VEGF and PDGF in nasal airway remodeling, and to assess the preventive effects of anti-angiogenic drugs on this process in a murine AR model.MethodsMice were systemically sensitized and subjected to inhalation of ovalbumin (OVA) twice a week for 3 months. Control mice were challenged with phosphate buffered saline, while the treatment group received SU1498, a VEGF receptor inhibitor, and/or AG1296, a PDGF receptor inhibitor, via intraperitoneal injection 4 hours prior to each OVA inhalation. Staining using hematoxylin and eosin, Masson's trichrome, and periodic acid-Schiff were separately performed to assess eosinophil infiltration, subepithelial fibrosis, and goblet cell hyperplasia, respectively, in the nasal airway. Immunohistochemical staining for matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) was also conducted.ResultsRepetitive intranasal inhalation of OVA resulted in significant increases in eosinophil infiltration, subepithelial fibrosis, goblet cell count, and MMP-9/TIMP-1 expression. Administration of SU1498 or AG1296 prevented these abnormal responses.ConclusionsThe results of this study suggest that a causal relationship may exist between angiogenic factors and nasal airway remodeling in AR. Inhibition of VEGF or PDGF receptors may, in turn, suppress the remodeling process through the regulation of MMP-9/TIMP-1 expression.

Peroxisome Proliferator‐Activated Receptor–γ Agonist Induces Regulatory T Cells in a Murine Model of Allergic Rhinitis

To evaluate the effects of peroxisome proliferator-activated receptor (PPAR)-γ agonist on the induction of regulatory T cells (Tregs) in a murine model of allergic rhinitis. Randomized controlled trial. Animal study. BALB/c mice that received ovalbumin sensitization and challenge served as the ovalbumin group (n = 6). Two separate groups of 6 mice received intragastric administration with PPAR-γ agonist pioglitazone (30 mg/kg/d) or pioglitazone plus PPAR-γ antagonist GW9662 (0.5 mg/d) before each ovalbumin challenge. The control group (n = 6) was treated with drug vehicle alone. Various allergic responses were assessed. Real-time polymerase chain reaction was performed to investigate the mRNA expression of forkhead box P3 (Foxp3), T-bet, and GATA-3. Flow cytometry was used to determine the percentage of Tregs. Mice developed typical pathophysiological allergic rhinitis features after the ovalbumin challenge. The frequencies of sneezing and scratching were significantly decreased by pioglitazone treatment (P < .0001). Eosinophils infiltration and the levels of interleukin-5 and interferon-γ in nasal cavity lavage fluid and sera immunoglobulin E were also markedly decreased by pioglitazone (P < .001). The expression of Foxp3 mRNA and the population of Tregs were significantly increased by pioglitazone (P < .05). Cotreatment with GW9662 reversed the anti-inflammatory effects of pioglitazone. The effects of PPAR-γ agonist on Foxp3 mRNA expression and Tregs induction were abrogated by administration of GW9662. PPAR-γ agonist attenuates upper airway allergic inflammation in a PPAR-γ-dependent fashion, and the beneficial effects of pioglitazone in airway allergic inflammation may be mediated by induction of Tregs.

Change of Th17 and expression of RORγt in a murine model of allergic rhinitis after a stimulation of allergen and corticosteroid

To study the effects of allergen and corticosteroid on T help 17 (Th17) and orphan nuclear receptor gammat (RORγt) in allergic-rhinitis mice. Experimental allergic rhinitis (AR) was induced by the extract of dermatophagoides pteronyssinus (DP) including 2% ovalbumin (OVA) sensitization in 30 male mice with DP allergen group (n = 10), intranasal corticosteroid (budesonide, BUD) group (n = 10) or without treatment (model group, n = 10). And another 10 were included into the normal control group. The murine levels of Th17 were measured by flow cytometry (FCM). The expression of RORγt mRNA was measured by reverse transcription-polymerase chain reaction (RT-PCR) while that of RORγt protein in nasal mucosa detected by immunohistochemical staining. The expression of RORγt in nasal mucosa of AR model was higher than that in the control group (25 ± 5 vs 48 ± 10, P < 0.01). But its expression declined significantly after the administration of local corticosteroid (48 ± 10 vs 31 ± 6, P < 0.01). The levels of RORγt mRNA and Th17 in the AR model group were significantly higher than those in the control group (18.4% ± 1.3% vs 27.5% ± 1.6%, 0.43 ± 0.04 vs 0.64 ± 0.05, both P < 0.01). The levels of RORγt mRNA and Th17 in the spleen of AR mice were significantly reduced by allergen dosing (27.5% ± 1.6% vs 20.0% ± 2.1%, 0.64 ± 0.05 vs 0.54 ± 0.03, both P < 0.01) but not by corticosteroid (P > 0.05). Allergen may affect the systemic immunity to inhibit the RORγt expression and block the Th17 differentiation in AR model. Local steroid only produces a marked effect through a down-regulated RORγt expression in nasal mucosa.

Sake Lees Fermented with Lactic Acid Bacteria Prevents Allergic Rhinitis-Like Symptoms and IgE-Mediated Basophil Degranulation

We tested the effect of oral administration of fermented sake lees with lactic acid bacteria (FESLAB) on a murine model of allergic rhinitis upon immunization and nasal sensitization with ovalbumin (OVA). We used Lactobacillus paracasei NPSRIk-4 (isolated from sake lees), and L. brevis NPSRIv-8 (from fermented milk) as starter strains to produce the FESLAB. Oral FESLAB administration resulted in the development of significantly fewer sneezing symptoms than those seen in sham control animals given sterile water. We also found that FESLAB suppressed the allergen-induced degranulation of RBL2H3 rat basophilic leukemia cells.