Nasal Mucosa In Allergic Rhinitis Research Articles

Microvascular remodeling of nasal mucosa in allergic rhinitis induced by an allergen in Sprague-Dawley rats

This study aimed to observe microvascular changes in the nasal mucosa of Sprague-Dawley (SD) rats with allergic rhinitis (AR) after persistent exposure to an allergen with fluticasone propionate (FP) treatment. Ninety healthy SD rats were randomly distributed into the control group (A, N = 30), the group with continued exposure to an allergen (B, N = 30), and FP treatment group (C, N = 30). The animals of the persistence group were subjected to persistent exposure to an allergen after 7 weeks of modeling of ovalbumin (OVA) provocation in the nasal mucosa for 16 weeks. At the 8th, 12th, and 16th week after OVA provocation, each group was euthanized at each time point: the FP treatment after OVA provocation, and animals of the control group were not stimulated with OVA and were sacrificed at the same time point. The nasal mucosa of 5 animals from each group was analyzed for the expression of vascular endothelial growth factor (VEGF), and another 5 animals were used to make micro vascular corrosion casts for a scanning electron microscope. The results demonstrate that FP has a strong inhibitory effect on angiogenesis in AR. Inhalation of FP had an antiangiogenic effect through inhibition of VEGF expression but does not completely reverse the remodeling of the nasal mucosa in the short term nor does it have complete control over the expression of VEGF mRNA.

Upregulation of Interleukin-35 Subunits in Regulatory T Cells in a Murine Model of Allergic Rhinitis

Objective: Regulatory T (Treg) cells play a critical role in the pathophysiology of allergic rhinitis (AR). We investigated the regulatory roles of interleukin (IL)-35, an immunosuppressive cytokine expressed by CD4⁺CD25⁺Foxp3⁺ Treg cells, in a murine model of AR. Methods: The expression of IL-35 subunits (Ebi3, encoded by Ebi3, and IL-12p35, encoded by IL12a) and IL-35 receptor chains (IL12rb and IL6st) in nasal mucosa and in spleen-derived Treg cells from ovalbumin (OVA)-sensitized AR was analyzed by immunohistochemistry and quantitative real-time RT-PCR techniques. Results: IL-35 subunit secretion was associated with local OVA sensitization in this murine model of AR. Ebi3 and IL-12p35, as well as CD3, were expressed differentially in the same regions of nasal mucosa of both AR and control animals. Ebi3 mRNA levels were significantly downregulated in the nasal mucosa of AR mice compared with control mice. Similarly, Ebi3 and IL12a mRNA levels were significantly upregulated in CD4⁺CD25⁺ Treg cells and, correspondingly, downregulated in CD4⁺CD25^- T effector (Teff) cells. IL6st mRNA levels were also significantly downregulated in CD4⁺CD25^- Teff cells. Conclusions: Decreased Ebi3 may have a crucial regulatory effect on the nasal mucosa in AR. The increased IL-35 subunit expression in CD4⁺CD25⁺ Treg cells may contribute to regulating the pathogenesis of AR. i 2014 S. Karger AG, Basel

Increased Expression of YKL-40 in Mild and Moderate/Severe Persistent Allergic Rhinitis and its Possible Contribution to Remodeling of Nasal Mucosa

Prominent expression of YKL-40 has been associated with pathological conditions characterized by tissue remodeling. We determined the expression level and distribution pattern of YKL-40 in allergic nasal mucosa and evaluated the effect of YKL-40 on the proliferation and migration of fibroblasts, the production of the mediators related to tissue remodeling, and collagen production. Additionally, the cytokine-driven regulation of YKL-40 expression was evaluated in cultured epithelial cells. The expression of YKL-40 in normal, mild, and moderate/severe allergic nasal mucosa was evaluated using real-time polymerase chain reaction (PCR), Western blot, and immunohistochemistry. Fibroblast migration was observed using a scratch wound method, and proliferation was determined by the MTT methods. Expression of proteoglycans, transforming growth factor (TGF) beta1, MMP2, MMP9, TIMP1, TIMP2, and collagen concentration were analyzed in fibroblasts treated with YKL-40. The expression levels of YKL-40 in cultured epithelial cells were examined after stimulation with mediators including Th2 cytokines, interferon (IFN)gamma, and TNF-alpha with real-time PCR and ELISA. The expression of YKL-40 was up-regulated in allergic rhinitis and distributed in superficial epithelium, submucosal glands, and vascular endothelium, in addition to infiltrating cells. TGF-beta1, TIMP1, MMP9, and biglycan were up-regulated in fibroblasts on stimulation with YKL-40, accompanying increased proliferation and migration, and collagen production. IL-13, IFN-gamma, and TNF-alpha induced the increased production of YKL-40 in cultured epithelial cells. YKL-40 is up-regulated in mild and moderate/severe persistent allergic rhinitis, and its expression can be regulated differentially by different cytokines, possibly contributing to the remodeling of nasal mucosa in allergic rhinitis.

Therapeutic potential of curcumin in experimentally induced allergic rhinitis in guinea pigs

In the present experiments, the possible role of curcumin in ovalbumin induced allergic rhinitis in guinea pig model was investigated. Various allergic rhinitis symptoms viz sneezing, rubbing frequencies, lacrimation and nasal congestion at various humidity conditions as well as on repeated sensitization were studied. The biochemical changes like serum IgE, IL-4 and nitric oxide (NO) in nasal lavage and eosinophil peroxidase activity in nasal homogenates were determined in allergic rhinitis. Curcumin treatment significantly reduced the symptoms (sneezing, rubbing frequencies, lacrimation and nasal congestion) and improved the histopathological alterations (reduction in inflammatory cells infiltration) of nasal mucosa in allergic rhinitis. Furthermore, curcumin treatment prevented significantly elevation of serum IgE, IL-4, NO in nasal lavage and eosinophil peroxidase in nasal homogenate. In the present experimental findings, we suggest that curcumin is a promising anti-allergic agent that may be useful in the clinical management of allergic rhinitis.

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.

Expressions of nuclear factor-kappa B p50 and p65 and their significance in the up-regulation of intercellular cell adhesion molecule-1 mRNA in the nasal mucosa of allergic rhinitis patients

The purpose of the study was to investigate expressions of nuclear factor-kappa B (NF-κB) and intercellular cell adhesion molecule-1 mRNA (ICAM-1 mRNA) in the nasal mucosa of allergic rhinitis (AR) patients. Expressions of NF-κB and ICAM-1 mRNA were studied using immunohistochemistry and reverse transcription-PCR (RT-PCR) in AR tissues and corresponding normal nasal mucosa. The correlation between NF-κB and ICAM-1 mRNA was studied using linear correlation analysis. The results of immunohistochemistry showed that expression of NF-κB was significantly up-regulated in the nasal mucosa of AR compared with that in normal tissue (P < 0.01), over-expression of NF-κB p50 was found in the cytoplasm and nucleus (P < 0.01), and NF-κB p65 was mainly expressed in the cytoplasm (P < 0.01). ICAM-1 mRNA was strongly expressed in the nasal mucosa of AR compared with that in normal tissue as shown by RT-PCR (P < 0.01). Up-regulation of ICAM-1 mRNA was significantly correlated with over-expressions of NF-κB p50 and NF-κB p65 (r = 0.8995, P < 0.01; r = 0.7601, P < 0.01). In conclusion, NF-κB plays a key role in AR. Excessively activated NF-κB promotes the transcription of ICAM-1 mRNA. ICAM-1 is related to the pathogenesis and development of AR.

B Cell Immunity in Allergic Nasal Mucosa Induces T helper 2 Cell Differentiation

The pathogenesis of allergic diseases is to be further understood. Recent studies indicate that B cells are involved in the immune regulation. The present study aimed to investigate the role of B cells in the initiation of skewed T helper (Th)2 polarization. The surgically removed nasal mucosal specimens from 24 patients with allergic rhinitis (AR) and 22 patients with non-AR (nAR) were collected. B cells isolated from the AR nasal mucosa were characterized. The effect of B cells on inducing naïve CD4+ T cells to differentiate into Th2 cells was evaluated with a cell culture model. Abundant B cells were detected in the nasal mucosa of patients with AR, which also expressed high levels of T cell immunoglobulin mucin domain (TIM)4 and costimulatory molecules. High levels of Staphylococcal enterotoxin B (SEB) were detected in the AR nasal mucosa. Expression of TIM4 could be induced in naïve B cells in the presence of SEB in culture. TIM4+ B cells could induce naïve CD4+ T cells to differentiate into Th2 cells. TIM4+ B cells from AR nasal mucosa can induce skewed Th2 polarization. It may be a potential therapeutic target in the treatment of AR. B cells plays an important role in the initiation of Th2 polarization. • High frequency of B cells exists in nasal mucosa of allergic rhinitis • These B cells express high levels of TIM4 • TIM4+ B cells can initiate the skewed Th2 polarization.

To study of the nasal mucosa remodeling of allergic rhinitis patients

To explore whether there was tissue remodeling in the nasal mucosa of allergic rhinitis (AR) patients and detect the protein expressions of transforming growth factor beta1 (TGF-beta1), matrix metalloproteinases 9 (MMP-9) and tissue inhibitors of matrix metalloproteinases 1 (TIMP-1) in the nasal mucosa of these patients. Pathologic staining was used to explore the mucosa of the middle turbinate tissues from 16 patients with mild AR, from 12 patients with severe AR, and from 15 non-AR, respect. The infiltrating of eosinophils and damage of epithelium were examined by the hematoxylin-eosin staining; goblet cells were counted by the alcian blue-periodic acid-schiff staining; the percentage area of extracellular matrix was determined by the MT; the protein expressions were measured by ELISA of TGF-beta1, MMP-9 and TIMP-1 in the middle turbinate tissues. Compared with the control group, significant eosinophil infiltration and goblet cells were observed in both AR groups (P < 0.05). Evident epithelial damage and extracellular matrix deposition were observed in severe-AR group (P < 0.05). The expressions of TGF-beta1, MMP-9 and TIMP-1 in AR tissues were significant increased (P < 0.05). The nasal mucosa remodeling was observed in AR groups. The characteristics were as follows: eosinophils infiltration, epithelial damage, goblet cells hyperplasia and extracellular matrix deposition. TGF-beta1, MMP-9, TIMP-1 may play a role in the tissue remodeling processes.

Luminal decoration of blood vessels by activated perivasal mast cells in allergic rhinitis

In allergic diseases, like in rhinitis, antigen challenge induces rapid degranulation of tissue resident mast cells and subsequent recruitment of leukocytes in response to soluble immunmodulators. The fate of mast cell-derived, membrane associated factors in inflamed tissue remained however unresolved. Components of the mast cell granular membrane, including the unique marker CD63var, were examined by FACS and by confocal laser scanning microscopy in cell culture and in diseased human tissue. We discovered that selected mast cell membrane components appeared on the surface of distinct bystander cells. Acceptor cells did not acquire these molecules simply by uptake of soluble material or in the form of exosomes. Instead, physically stable cell-to-cell contact was required for transfer, in which a Notch2-Jagged1 interaction played a decisive role. This process is activation-dependent, unidirectional, and involves a unique membrane topology. Endothelial cells were particularly efficient acceptors. In organotypic 3D in vitro cultures we found that transferred mast cell molecules traversed an endothelial monolayer, and reappeared focally compacted on its distal surface, away from the actual contact zone. Moreover, we observed that such mast cell-derived membrane patches decorate microcapillaries in the nasal mucosa of allergic rhinitis patients. Direct membrane transfer from perivasal mast cells into nearby blood vessels constitutes a novel mechanism to modulate endothelial surface features with apparent significance in allergic diseases.

Effects of Repetitive Allergen Challenge on Expression of TGF-β, Activin -A and Its Receptor ALK4 in Nasal Mucosa of Allergic Rhinitis

RationaleTransforming growth factor (TGF)-β and activin-A are implicated in the airway remodelling in asthma, but the role in allergic rhinitis (AR) has not been elucidated. We aimed to determine the expression of TGF-β, activin-A and its receptor activin-like kinase 4 (ALK-4) in nasal mucosa of allergic rhinitis after repetitive allergen challenge.Methods12 subjects with grass pollen-associated seasonal AR and 16 normal health controls have been studied, repetitive allergen challenge(RAC) and diluents were given the allergic patients and health groups for the total 5 doses, two biopsies were taken after 24 hours at the first (Day1) and last challenge (Day11). Immunoreactivity of Activin-A, ALK-4 and TGF-β in the biopsies was assessed by immunohistochemistry and image analysis.ResultsThere were significant higher in the numbers of Activin-A and TGF- β immunoreactive cells at day 11 after repetitive allergen challenge compared to diluents (Median [IQ range]: 43.4 (18.2-69.3) vs. 11.2 (2.9-37.5); p=0.01 for Activin-A, 29.7 (6.6-40.3) vs. 6.6 (1.2-12.3); p=0.04 for TGF-β respectively), the numbers of ALK-4 immunoreactive cells at day 11 were trend to increase compared to diluents (Median [IQ range]: 5.9 (1.3-16.4) vs. 1.4 (0.8-2.9); p=0.06). However, no significant differences in immunoreactivity of these molecules in nasal biopsies were found either between diluents and allergen challenge at day1, or compared with that of the healthy controls.ConclusionsOur data suggest that repetitive allergen challenge enhances the expression of activin-A and TGF-β in nasal mucosa of allergic rhinitis. These molecules may contribute to upper airway inflammation and remodelling in allergic rhinitis. RationaleTransforming growth factor (TGF)-β and activin-A are implicated in the airway remodelling in asthma, but the role in allergic rhinitis (AR) has not been elucidated. We aimed to determine the expression of TGF-β, activin-A and its receptor activin-like kinase 4 (ALK-4) in nasal mucosa of allergic rhinitis after repetitive allergen challenge. Transforming growth factor (TGF)-β and activin-A are implicated in the airway remodelling in asthma, but the role in allergic rhinitis (AR) has not been elucidated. We aimed to determine the expression of TGF-β, activin-A and its receptor activin-like kinase 4 (ALK-4) in nasal mucosa of allergic rhinitis after repetitive allergen challenge. Methods12 subjects with grass pollen-associated seasonal AR and 16 normal health controls have been studied, repetitive allergen challenge(RAC) and diluents were given the allergic patients and health groups for the total 5 doses, two biopsies were taken after 24 hours at the first (Day1) and last challenge (Day11). Immunoreactivity of Activin-A, ALK-4 and TGF-β in the biopsies was assessed by immunohistochemistry and image analysis. 12 subjects with grass pollen-associated seasonal AR and 16 normal health controls have been studied, repetitive allergen challenge(RAC) and diluents were given the allergic patients and health groups for the total 5 doses, two biopsies were taken after 24 hours at the first (Day1) and last challenge (Day11). Immunoreactivity of Activin-A, ALK-4 and TGF-β in the biopsies was assessed by immunohistochemistry and image analysis. ResultsThere were significant higher in the numbers of Activin-A and TGF- β immunoreactive cells at day 11 after repetitive allergen challenge compared to diluents (Median [IQ range]: 43.4 (18.2-69.3) vs. 11.2 (2.9-37.5); p=0.01 for Activin-A, 29.7 (6.6-40.3) vs. 6.6 (1.2-12.3); p=0.04 for TGF-β respectively), the numbers of ALK-4 immunoreactive cells at day 11 were trend to increase compared to diluents (Median [IQ range]: 5.9 (1.3-16.4) vs. 1.4 (0.8-2.9); p=0.06). However, no significant differences in immunoreactivity of these molecules in nasal biopsies were found either between diluents and allergen challenge at day1, or compared with that of the healthy controls. There were significant higher in the numbers of Activin-A and TGF- β immunoreactive cells at day 11 after repetitive allergen challenge compared to diluents (Median [IQ range]: 43.4 (18.2-69.3) vs. 11.2 (2.9-37.5); p=0.01 for Activin-A, 29.7 (6.6-40.3) vs. 6.6 (1.2-12.3); p=0.04 for TGF-β respectively), the numbers of ALK-4 immunoreactive cells at day 11 were trend to increase compared to diluents (Median [IQ range]: 5.9 (1.3-16.4) vs. 1.4 (0.8-2.9); p=0.06). However, no significant differences in immunoreactivity of these molecules in nasal biopsies were found either between diluents and allergen challenge at day1, or compared with that of the healthy controls. ConclusionsOur data suggest that repetitive allergen challenge enhances the expression of activin-A and TGF-β in nasal mucosa of allergic rhinitis. These molecules may contribute to upper airway inflammation and remodelling in allergic rhinitis. Our data suggest that repetitive allergen challenge enhances the expression of activin-A and TGF-β in nasal mucosa of allergic rhinitis. These molecules may contribute to upper airway inflammation and remodelling in allergic rhinitis.

The effect of intranasal steroid on nasal mucosa in rat model of allergic rhinitis

To investigate the effects of intranasal steroid on nasal mucosa in rat model of allergic rhinitis (AR). Thirty-six SD rats were randomly divided into three groups (each included 12 rats): the intranasal steroid group(group A),the allergic rhinitis group(group B) and the normal control group(group C). AR model was reproduced by ovalbumin in group A and B. The control group was allergized by NS instead of ovalbumin. Group A was used steroid spray in nasal and Group B and C was used normal saline. Then ,after the last provocation,the allergic symptoms were evaluated,the number of eosinophil (EOS) of the rats' nasal mucosa was counted under hematoxylineosin staining and the goblet cells was counted under alcian blue-periodic acid-Schiff staining. The morphological changes of the rats' nasal mucosa were observed by scanning electron microscope. Compared with group B,the inhibition of nasal symptoms was found after used of steroid spray in group A. The EOS and the goblet cells in group A was significantly different with that in Group B (P < 0.05), but no significant differences compared with group C (P > 0.05). Observed by scanning electron microscope, the cilia of the epithelium in group B were significantly lodging, disoriented, winding and secreting,while the cilia of the epithelium in Group A and C had similar appearance. Intranasal steroid spray can relieve symptoms and inflammatory conditions of nasal mucosa in allergic rhinitis, and can repair injured nasal mucosa cilia.

Angiogenic Factors Play a Significant Role in Nasal Airway Remodeling in Allergic Rhinitis

Angiogenic Factors Play a Significant Role in Nasal Airway Remodeling in Allergic Rhinitis

Eosinophilic Inflammation in Allergic Rhinitis and Nasal Polyposis

On histopathological examination, nasal polyps and nasal mucosa in allergic rhinitis show different forms of pseudostratified respiratory epithelium, whereas the dominant characteristic of lamina propria is an eosinophilic infiltration. The aim of this study was to compare interleukin (IL)-5 and eosinophilic cationic protein (ECP) levels in the nasal fluid of 42 patients: 12 with allergic rhinitis and nasal septal deviation, 17 non-atopic patients with nasal polyposis, and 13 atopic nasal polyp patients were enrolled in this cross-sectional study. Nasal secretion samples were collected a few days before surgery. The levels of IL-5 were measured using flow cytometry and the ECP using a commercial ELISA kit. In addition, we counted eosinophils in hematoxylin-and-eosin-stained sections of all nasal polyp and all nasal mucosa samples taken from the inferior nasal turbinates during septoplasty. A significantly higher concentration of IL-5 was found in the nasal fluid of atopic patients with nasal polyposis than in non-atopic nasal polyp patients (p=0.025) and patients with allergic rhinitis (p=0.05). ECP was higher in atopic nasal polyp patients than in patients with allergic rhinitis (p<0.0001) and than in non-atopic nasal polyp patients (p<0.0001). Polyp eosinophils were higher in atopic' than in non-atopic patients (p<0.0001) and higher than in the mucosa of patients with allergic rhinitis (p<0.0001). These however had significantly more mucosal eosinophils than was found in the polyps of non-atopic patients' (p=0.025). ECP levels in nasal fluid and eosinophil counts in tissue specimens correlated well in all three groups of patients. Our study has shown that atopic nasal polyp patients have a higher level of eosinophilic inflammation than non-atopic patients with nasal polyps and patients with allergic rhinitis.

Regulatory-T, T-Helper 1, and T-Helper 2 Cell Differentiation in Nasal Mucosa of Allergic Rhinitis with Olive Pollen Sensitivity

Background: Allergic rhinitis (AR) is a disease in which T-helper (Th)2 response is predominant and its pathogenic mechanism is still poorly understood. Aim: To evaluate the possible role of Th1, Th2 and regulatory-T (Treg) cells in the pathogenesis of AR. Methods: This case-control study enrolled 41 patients with seasonal AR (10–62 years old), sensitive to olive pollens, and 15 healthy controls (18–60 years old). Nasal biopsy was performed and specimens of nasal lavage fluid were obtained from all participants. The levels of interleukin (IL)-4, IL-10, interferon (IFN)-γ and transforming growth factor-β (TGF-β) were measured in nasal lavage fluid specimens. The expression of FOXP3, GATA-3 and T-bet was measured by immunohistochemical methods in the nasal biopsy specimens. Results: The levels of IFN-γ in the group with AR were significantly lower than those in the control group (p = 0.008). The levels of IL-4, IL-10 and TGF-β did not differ between the two groups. The expression of FOXP3 and T-bet in patients with AR was significantly lower than that in the control group (both p = 0.001). Expression of GATA-3 in the nasal mucosa was similar between the groups (p = 0.2). The ratios of T-bet/GATA-3 and FOXP3/GATA-3 in the AR group were significantly lower than those in the control group (p = 0.001). Conclusion: Insufficient Treg and Th1 cells may be associated with the allergic inflammation that may be attributed to the Th2 immune response in patients suffering from AR who are sensitive to olive pollen.

The role of IL‐33 and its receptor ST2 in human nasal epithelium with allergic rhinitis

Interleukin (IL)-33 is a novel member of the IL-1 cytokine family and a ligand for the orphan IL-1 family receptor ST2. The IL-33 induces T helper 2-type inflammatory responses and is considered to play a crucial rule in allergic inflammations, such as asthma and atopic dermatitis. However, the role of IL-33 and its receptor ST2 in allergic rhinitis remains unknown. We investigated expression of IL-33 and ST2 in the nasal epithelium of patients with allergic rhinitis and the mechanisms of the production of cytokines/chemokines induced by treatment with IL-33 using normal human nasal epithelial cells (HNECs) in vitro. Expression of IL-33 and ST2 in normal and allergic rhinitis nasal mucosa was evaluated by reverse transcription- and real-time polymerase chain reactions and immunohistochemical methods. The IL-33 in serum, and IL-8 and GM-CSF were measured by ELISA. For in vitro experiments, HNECs in primary culture were used. The IL-33 levels in the sera of patients with allergic rhinitis were significantly higher than that in normal controls. Expression of IL-33 and ST2 was significantly elevated in the epithelium from patients with allergic rhinitis. The IL-33 mRNA in HNECs in vitro was significantly induced by treatment with IFN-γ and the toll-like receptor 9 ligand ODN2006. The IL-33-induced production of IL-8 and GM-CSF from HNECs in vitro was significantly suppressed by corticosteroid treatment and distinct signal transduction inhibitors of ERK, p38 MAPK, JNK, NF-κB and epidermal growth factor receptor. The IL-33 and its receptor ST2 play important roles in allergic rhinitis. The IL-33-mediated inflammatory responses via ST2 are regulated by distinct signalling pathways in HNECs and the IL-33/ST2 pathway may provide new therapeutic targets for allergic rhinitis.

Staphylococcal enterotoxin B compromises the immune tolerant status in the airway mucosa

The breakdown of immune tolerance plays a critical role in allergic disorders; the mechanism of breaching immune tolerance remains largely unknown. The present study aimed to investigate the role of Staphylococcal enterotoxin B (SEB) in the interference of the immune tolerance in the nasal mucosa. The immune tolerant components, tolerogenic dendritic cells (TolDC) and regulatory T cells (Treg), were assessed in the surgically removed nasal mucosa from patients with allergic rhinitis (AR) or non-AR chronic rhinitis. The contents of SEB and integrin alphavbeta6 (avb6) in the nasal epithelium were assessed using enzyme-linked immunoassay. The ability of avb6 on TolDC induction and the effect of SEB on suppression of avb6 in nasal epithelial cells were observed in cell culture. Compared with that in the non-AR nasal mucosa, the frequencies of TolDCs/Tregs were lower, the contents of SEB were higher and the contents of avb6 were lower in the AR nasal mucosa. Avb6 had the ability to induce the development of TolDCs in vitro; the latter had the ability to induce Treg development. The expression of avb6 was detected in nasal epithelial cells in culture that could be suppressed by SEB. The components of immune tolerance machinery, TolDCs and Tregs were suppressed in the AR nasal mucosa. The increases in SEB and decreases in avb6 in nasal epithelium are associated with the compromises of immune tolerance in the nasal mucosa. SEB has the ability to suppress the expression of avb6 in nasal epithelial cells.

Experimentally induced accumulation of Foxp3+ T cells in upper airway allergy

It has been suggested that Foxp3(+) regulatory T (Treg) cells inhibit allergic inflammation in humans by suppressing the activation of allergen-specific effector T cells. Whether this occurs at the site of allergen exposure has not been determined. To determine the occurrence of Foxp3(+) Treg cells in the nasal mucosa of allergic rhinitis (AR) patients and non-allergic controls after a nasal allergen challenge. Pollen-allergic patients (n=18) and non-allergic volunteers (n=7) were challenged locally with pollen extract or placebo for 7 days outside the pollen season. Mucosal biopsies were obtained from the inferior turbinate on days 0, 1 and 7 and subjected to multi-colour immunofluorescence and blood was drawn for eosinophil counts on days 0, 2, 5 and 7. Only AR patients receiving pollen extract experienced typical allergic symptoms and demonstrated increased levels of eosinophils in peripheral blood and nasal mucosa. In allergic patients, a transient early increase (day 1) in CD3(+) T cells was observed in the nasal mucosa, followed by a significant increase of Foxp3(high) T cells at day 7. No changes were found in the control group. The majority of Foxp3(high) cells co-expressed CTLA-4, CD25 and CD4, and a substantial fraction expressed the proliferation marker Ki67. Experimentally induced inflammation in AR patients leads to an early inflammatory response followed by accumulation of Foxp3(high) T cells in the nasal mucosa. Our findings are similar to that observed in allergic airways of experimental mice, which suggest that Treg cells are operative in allergic upper airway inflammation. It should be explored whether Treg cells accumulating in the nasal mucosa could be targets for therapeutic intervention.

Antioxidant Status and Immune Activity of Glycyrrhizin in Allergic Rhinitis Mice

Oxidative stress is considered as a major risk factor that contributes to increased lipid peroxidation and declined antioxidants in some degenerative diseases. Glycyrrhizin is widely used to cure allergic diseases due to its medicinal properties. In the present study, we evaluated the role of glycyrrhizin on lipid peroxidation and antioxidant status in the blood and nasal mucosa of allergic rhinitis (AR) mice. Mice were divided into six groups: normal control mice, model control (MC) mice, three glycyrrhizin-treated mice groups and lycopene-treated mice. Sensitization-associated increase in lipid peroxidation was observed in the blood and nasal mucosa of MC mice. Activities of antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), total antioxidant capacity (TAOC) and levels of glutathione (GSH) were found to be significantly decreased in the blood and nasal mucosa in MC mice when compared to normal control mice. However, normalized lipid peroxidation and antioxidant defenses were reported in the glycyrrhizin-treated and lycopene-treated mice. Moreover, glycyrrhizin treatment still enhanced IFN-γ and reduced IL-4 levels in glycyrrhizin-treated mice. These findings demonstrated that glycyrrhizin treatment enhanced the antioxidant status and decreased the incidence of free radical-induced lipid peroxidation and improved immunity activities in the blood and nasal mucosa of AR mice.

Increased Expression and Role of Thymic Stromal Lymphopoietin in Nasal Polyposis

PurposeNasal polyposis is a chronic inflammatory disease of the upper airways often associated with asthma and characterized by markedly increased numbers of eosinophils, Th2 type lymphocytes, fibroblasts, goblet cells and mast cells. Previous studies have shown elevated levels of thymic stromal lymphopoietin (TSLP) in atopic diseases like asthma, atopic dermatitis and mainly in animal models of allergic rhinitis (AR). Here, we investigated the expression of TSLP in nasal polyps from atopics and non-atopics in comparison with the nasal mucosa and its potential role in nasal polyposis.MethodsMessenger RNA expression for TSLP, thymus and activation-regulated chemokine (TARC) and macrophage derived chemokine (MDC) in nasal polyps and nasal mucosa of atopics and non-atopics was analyzed by real time PCR. Immunoreactivity for TSLP in nasal polyps and in the nasal mucosa of patients with AR and non-allergic rhinitis (NAR) was analyzed by immunohistochemistry. Eosinophil counts was analyzed by Wright-Giemsa staining and nasal polyp tissue IgE, by ELISA.ResultsMessenger RNA expression for TSLP,TARC and MDC was markedly higher in nasal polyps as compared to the allergic nasal mucosa. Immunoreactivity for TSLP was detected in epithelial cells, endothelial cells, fibroblasts and inflammatory cells of the nasal mucosa and nasal polyps. The number of TSLP+ cells was significantly greater in the nasal mucosa of AR than NAR patients. The number of TSLP+ cells in nasal polyps from atopics was significantly greater than that of non-atopics and that in the allergic nasal mucosa. The number of TSLP+ cells correlated well with the number of eosinophils and the levels of IgE in nasal polyps.ConclusionsThe high expression of TSLP in nasal polyps and its strong correlation to eosinophils and IgE suggest a potential role for TSLP in the pathogenesis of nasal polyps by regulating the Th2 type and eosinophilic inflammation.

TGF-β Signaling May Play a Role in the Development of Goblet Cell Hyperplasia in a Mouse Model of Allergic Rhinitis

Transforming growth factor-beta (TGF-beta) levels are elevated in the nasal mucosa in allergic rhinitis. However, because TGF-beta is secreted extracellulary in latent complexes, it remains unclear whether the local TGF-beta expression actually drives active signaling and affects the pathophysiology of allergic rhinitis. The objective of this study is to investigate whether TGF-beta signaling is activated in allergic rhinitis and plays a role in the pathophysiology of allergic rhinitis. An ovabumin (OVA)-sensitized and -nasally challenged mouse model of allergic rhinitis was established and phosphorylation of Smad2 in the nasal mucosa was examined by immunohistochemistry. In addition, the effects of the pharmacological inhibition of endogenous TGF-beta signaling on the allergic rhinitis model were histologically examined. Furthermore, phosphorylation of Smad2 in the nasal mucosa samples obtained from patients with allergic rhinitis was also evaluated. In the mouse model of allergic rhinitis, OVA challenge induced phosphorylation of Smad2 predominantly in epithelial cells in the nasal mucosa. In addition, the administration of an inhibitor of TGF-beta type I receptor kinase activity during OVA challenge suppressed goblet cell hyperplasia in the nasal mucosa. Furthermore, phosphorylated Smad2 expression increased in nasal epithelial cells in patients with allergic rhinitis. These results suggest that TGF-beta signaling is activated in epithelial cells in the nasal mucosa in allergic rhinitis and may contribute to the development of goblet cell hyperplasia.