Rat Model Of Allergic Rhinitis Research Articles

ROS responsive hydrogel for inhibition of MUC5AC against allergic rhinitis: A new delivery strategy for Ipratropium Bromide

Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa mediated by immunoglobulin E (IgE) after exposure to allergens. The bothersome symptoms of AR, such as runny nose and nasal congestion, affect millions of people worldwide. Ipratropium Bromide (IB), commonly used in clinical practice for treating AR, requires frequent administration through nasal spray and may cause significant irritation to the nasal mucosa. The induction of ROS is closely related to the initiation and symptoms of AR, and ROS will continue to accumulate during the onset of AR. To address these challenges, we have designed a drug delivery system that can be administered in liquid form and rapidly crosslink into a ROS-responsive gel in the nasal cavity. This system enables sustained ROS responsive release of IB in a high-concentration ROS environment at AR lesions, thereby alleviating AR symptoms. The gel demonstrated prolonged release of IB for up to 24 hours in rats. In the treatment of AR rat models, it improved their symptoms, reduced the expression of various inflammatory factors, suppressed MUC5AC protein expression, and decreased mucus secretion through a ROS responsive IB release pattern. Overall, this system holds promise as a better option for AR treatment and may inspire the design of nanogel-based nasal drug delivery systems.

Acupuncture at "Die E acupoint" alleviates inflammatory reaction via inhibiting TLR4/MyD88/NF-κB signaling in rats with allergic rhinitis.

To observe effects of acupuncture at "Die E acupoint" on the protein expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear transcription factor κB (NF-κB), transcription factor T-bet (T-bet), and GATA-binding protein-3 (GATA-3) in the nasal mucosa and the serum contents of related inflammatory cytokines in rats with allergic rhinitis, so as to explore the mechanism of acupuncture in treating allergic rhinitis. Twenty-four healthy SD rats were randomly divided into blank, model, acupuncture, and sham acupuncture groups, with 6 rats in each group. The rat model of allergic rhinitis was established by using ovalbumin induction. The rats in the acupuncture group received bilateral acupuncture at the "Die E acupoint" with a depth of 15-20 mm, while the rats in the sham acupuncture group received only sham acupuncture (light and shallow acupunture of the skin at the "Die E acupoint" ). Both interventions were performed once daily for a total of 6 days. Behavioral scores of rats in each group were recorded. Pathological changes of nasal mucosa were observed by H.E. staining. Serum contents of IgE, ovalbumin-specific IgE (OVA-sIgE), interferon(IFN)-γ, interleukin(IL)-4, IL-10 and IL-17 were measured by ELISA and the protein expression levels of T-bet, GATA-3, TLR4, MyD88 and NF-κB p65 in the nasal mucosa were detected by Western blot. After modeling, compared with the blank group, rats in the model group showed increased behavioral scores, serum IgE, OVA-sIgE, IL-4, and IL-17 contents, and nasal mucosal GATA-3, TLR4, MyD88, and NF-κB p65 protein expression levels (P<0.05), whereas the contents of serum IFN-γ, IL-10 and the protein expression level of T-bet in the nasal mucosa were decreased (P<0.05). Comparison between the EA and model groups showed that acupuncture intervention can decrease the behavioral scores of rats with allergic rhinitis, the contents of serum IgE, OVA-sIgE, IL-4, IL-17, and the protein expression levels of GATA-3, TLR4, MyD88, and NF-κB p65 in the nasal mucosa (P<0.05), and up-regulate the contents of serum IFN-γ, IL-10, and the nasal mucosal T-bet protein expression level. Sham acupuncture did not have a significant modulating effect on the above indicators. Inflammatory infiltration of nasal mucosa was seen in the model group and sham acupuncture, and the inflammatory reaction was milder in the acupuncture group. Acupuncture at "Die E acupoint" can alleviate the symptoms of allergic rhinitis and suppress the inflammation of nasal mucosa in rats, which may be related to inhibiting the TLR4/MyD88/NF-κB signaling and balancing the levels of cytokines of Th1/Th2 and Treg/Th17, and T-bet/GATA-3.

Cang-ai volatile oil alleviates nasal inflammation via Th1/Th2 cell imbalance regulation in a rat model of ovalbumin-induced allergic rhinitis.

We previously revealed that Cang-ai volatile oil (CAVO) regulates T-cell activity, enhancing the immune response in people with chronic respiratory diseases. However, the effects of CAVO on allergic rhinitis (AR) have not been investigated. Herein, we established an ovalbumin (OVA)-induced AR rat model to determine these effects. Sprague-Dawley (SD) rats were exposed to OVA for 3weeks. CAVO or loratadine (positive control) was given orally once daily for 2weeks to OVA-exposed rats. Behavior modeling nasal allergies was observed. Nasal mucosa, serum, and spleen samples of AR rats were analyzed. CAVO treatment significantly reduced the number of nose rubs and sneezes, and ameliorated several hallmarks of nasal mucosa tissue remodeling: inflammation, eosinophilic infiltration, goblet cell metaplasia, and mast cell hyperplasia. CAVO administration markedly upregulated expressions of interferon-γ, interleukin (IL)-2, and IL-12, and downregulated expressions of serum tumor necrosis factor-α, IL-4, IL-5, IL-6, IL-13, immunoglobulin-E, and histamine. CAVO therapy also increased production of IFN-γ and T-helper type 1 (Th1)-specific T-box transcription factor (T-bet) of the cluster of differentiation-4+ T-cells in splenic lymphocytes, and protein and mRNA expressions of T-bet in nasal mucosa. In contrast, levels of the Th2 cytokine IL-4 and Th2-specific transcription factor GATA binding protein-3 were suppressed by CAVO. These cumulative findings demonstrate that CAVO therapy can alleviate AR by regulating the balance between Th1 and Th2 cells.

H3 Receptor Expression in the Spinal Trigeminal Nucleus Caudalis in a Rat Model of Allergic Rhinitis

Background: Allergic rhinitis is one of the most frequently observed allergic diseases. Although antihistamine medication is an effective symptomatic treatment for this disease, it is not suffcient enough to improve quality of life, requiring an additional treatment. Excessive sneezing is a typical symptom of allergic rhinitis in response to immunological release of histamine, and we hypothesized that this could be due to characteristic changes on the reflex pathway, particularly a nucleus receiving nasal trigeminal afferents, the spinal trigeminal nucleus caudalis (Sp5C), via a histamine mechanism(s). In the present study, we created an allergic rhinitis model by conventional methods, harvesting brainstem tissues to perform immunohistochemistry for histamine receptor subtype 3 (H3R) in Sp5C. Methods: Male Fisher 344 rats (8 weeks old) were sensitized and nasally challenged to Ovalbumin. After the Ovalbumin challenge into the nasal cavity, the number of sneezing was visually counted for 13 min and repeated for 7 days. After that, animals were euthanized, brainstems were extracted, and immunohistochemistry were performed with various antibodies, including anti-H3R and -GFAP. In some animals, to identify the subregion within Sp5C where nasal trigeminal afferents are transmitted from the nasal mucosa, capsaicin (0.3mM), a potent nociceptive substance, was administered into the nasal cavity and then immunohistochemistry of c-Fos expression was performed. Quantitative analysis was performed by area of fluorescent staining. Results: Intranasal administration of capsaicin markedly increased c-Fos expression in Sp5C compared to non-administration control, confirming the subregion of Sp5C receiving nasal afferent information. The allergic rhinitis model rats showed a significant increase in sneezing frequency in response to Ovalbumin nasal challenge compared to non-sensitized rats challenged with Ovalbumin or saline (56.8±3.9 vs. 16.6±1.6 vs. 23.7±3.2 [sneezes during a total observation period]; p&lt;0.001). The expression pattern of H3Rs was punctate and co-stained with GFAP in many cases. Both H3 receptor and GFAP expressions were significantly decreased in allergic model rats compared to control rats (control vs. allergic; 21.2±1.2 vs.6.4±0.5 [%] in H3Rs, p&lt;0.001; 16.2±0.5 vs.10.9±0.8 [%] in GFAP, p&lt;0.001). No difference in DAPI staining was observed (14.5±0.8 vs.13.7±0.5 [%], p=0.223), suggesting similar population of cells in data analyzed from both groups. Discussion: These results may suggest that Sp5C is part of the sneezing reflex pathway and that a decrease in H3Rs, including those on astrocytes, is involved in worsening clinical symptoms of allergic rhinitis such as excessive sneezing. This research was supported by KAKENHI, Grant-in-Aid for challenging Exploratory Research # 21K19182. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

DIA-based quantitative proteomics analysis of plasma exosomes in rat model of allergic rhinitis

Allergic rhinitis (AR) is a common chronic inflammatory disease characterized by symptoms such as itching, rhinorrhea, sneezing, and nasal obstruction. Despite being classified as an IgE-mediated typeⅠ allergy for many years, the complex pathophysiological mechanism of AR continues to present a challenge in clinical management. The objective of this study was to quantify the proteomics of plasma exosomes using data independent acquisition (DIA) in combination with liquid chromatography-mass spectrometry (LC-MS/MS) to identify the key proteins involved in the development and progression of AR. In the AR rat model, a total of 41 proteins demonstrated significant up-regulation, while 51 proteins were found to be significantly down-regulated. Gene ontology (GO) analysis results indicated that the altered proteins were highly enriched in cellular regulatory processes and enzymatic activity in AR rats. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction (PPI) network results revealed that the pivotal proteins C4b, C1qa, C1qc, and Mbl1 might be involved in the metabolic pathways of the immune system in AR through the activation of the complement and coagulation cascades pathway. These proteins could serve as diagnostic markers and therapeutic targets for AR, which is of great significance in understanding the role of exosome proteins in AR.

Immunofluorescent Labeling in Nasal Mucosa Tissue Sections of Allergic Rhinitis Rats via Multicolor Immunoassay.

Allergic rhinitis (AR) is a chronic, non-infectious inflammatory disease of the nasal mucosa, primarily mediated by specific immunoglobulin E (IgE), affecting approximately 10%-20% of the world's population. While immunofluorescence (IF) staining has long been a standard technique for detecting disease-specific protein expression, conventional IF techniques are limited in their ability to detect the expression levels of three or more proteins in the same sample. Consequently, multicolor IF techniques have been developed in recent years, which allow the simultaneous labeling of multiple targets in cells or tissues. This protocol provides a comprehensive overview of the process for establishing a rat model of AR, obtaining nasal mucosal samples, and the technical procedures for multicolor immunofluorescence. All rats in the AR group exhibited typical symptoms such as sneezing, a runny nose, and an itchy nose, with behavioral observations scoring ≥5 points. Hematoxylin and eosin (H&E) staining revealed increased inflammatory cell counts and disrupted nasal mucosal integrity in the AR group. Multicolor immunofluorescence (mIF) demonstrated increased expression of RORγt and TICAM-1, while Foxp3 expression decreased in the nasal mucosa tissue of AR rats.

Human placental extract regulates polarization of macrophages via IRGM/NLRP3 in allergic rhinitis

Allergic rhinitis (AR) is globally prevalent and its pathogenesis remains unclear. Alternative activation of macrophages is suggested in AR and thought to be involved in natural immunoregulatory processes in AR. Aberrant activation of Nod-like receptor protein 3 (NLRP3) inflammasome is linked with AR. Human placenta extract (HPE) is widely used in clinics due to its multiple therapeutic potential carried by diverse bioactive molecules in it. We aim to investigate the effect of HPE on AR and the possible underlying mechanism. Ovalbumin (OVA)-induced AR rat model was set up and treated by HPE or cetirizine. General manifestation of AR was evaluated along with the histological and biochemical analysis performed on rat nasal mucosa. A proteomic analysis was performed on AR rat mucosa. Mouse alveolar macrophages (MH-S cells) were cultured under OVA stimulation to investigate the regulation of macrophages polarization. The morphological changes and the expression of NLRP3 inflammasome and immunity-related GTPase M (IRGM) in nasal mucosa as well as in MH-S cells were evaluated respectively. The results of our study showed the general manifestation of AR along with the histological changes in nasal mucosa of AR rats were improved by HPE. HPE suppresses NLRP3 inflammasome and the decline of IRGM in AR rats and MH-S cells. HPE regulates macrophage polarization through IRGM/NLRP3. We demonstrated that HPE had protection for AR and the protection is achieved partly through suppressing M1 while promoting M2, the process which is mediated by IRGM via inhibiting NLRP3 inflammasome in AR.

Atorvastatin attenuates allergic inflammation by blocking prostaglandin biosynthesis in rats with allergic rhinitis.

Prostaglandins (PGs) are bioactive lipid mediators derived from the nuclear and plasma membranes via the cyclooxygenase (COX) pathway of arachidonic acid (AA) metabolism. PGs bridge the interactions between various immunomodulatory cells in allergic rhinitis (AR) and are considered key players in regulating pro-inflammatory and anti-inflammatory responses. AA conversion to PGs involves rate-limiting enzymes that may be blocked by statins. The mechanisms by which statins regulate these enzymes in AR remain unclear. We investigated the effects of oral atorvastatin on PGs production in AR. An ovalbumin-induced AR rat model was constructed and the changes in nasal symptom score and nasal mucosa histopathological characteristics of AR rats under different atorvastatin doses were assessed. qRT-PCR, western blotting, and immunofluorescence were used to detect the mRNA and protein expression levels of rate-limiting enzymes and downstream molecules of AA metabolism in the nasal mucosa and liver. Oral atorvastatin significantly alleviated symptoms and eosinophil infiltration in the nasal mucosa, inhibited goblet cell hyperplasia and mast cell recruitment, and decreased mucus secretion in AR rats. Increasing atorvastatin dose increased the anti-inflammatory effects. High-dose atorvastatin inhibited upregulation of the inflammatory mediator PGD2 in the nasal mucosa of AR rats. Compared to the control group, the mRNA and protein expression of the rate-limiting enzymes COX-2, PGDS, and PGES in AA metabolism in the AR group were upregulated but downregulated after the oral administration of high-dose atorvastatin. Atorvastatin also showed dose-dependent inhibition of ERK1/2 and downstream NF-κB phosphorylation in the nasal mucosa and liver of AR rats. Atorvastatin inhibited allergic inflammation and attenuated AR nasal symptoms by downregulating PGD2 and rate-limiting enzyme expression in PGD2 biosynthesis, possibly by blocking the RAS/ERK/NF-κB signaling pathway.

ESP-B4 promotes nasal epithelial cell-derived extracellular vesicles containing miR-146a-5p to modulate Smad3/GATA-3 thus relieving allergic rhinitis: ESP-B4/miR-146a-5p in AR

BackgroundThough generally a mild affliction, allergic rhinitis (AR) is very common and causes considerable discomfort. Ephedra sinica polysaccharide is a candidate cost-effective therapy to relieve AR symptoms. PurposeWe explore the molecular mechanism of pure polysaccharide ESP-B4 action in AR. MethodsRPMI2650 cells were treated with lipopolysaccharide to induce an in vitro sensitization model, and extracellular vesicles (EVs) were isolated. A rat model of AR was established using ovalbumin as the allergen and was treated with Ephedra sinica polysaccharide to observe changes in rhinitis symptoms, nasal mucosa histopathology and molecular pathology. ESP-B4-treated sensitized cells were adopted in vitro to verify effect of Ephedra sinica polysaccharide on miR-146a-5p expression in RPMI2650 cell-derived EVs and helper T cell differentiation. ResultsmiR-146a-5p inhibited Smad3, impeded the Smad3/GATA-3 interaction, upregulated IFN-γ expression, and promoted CD4+T cell Th1 differentiation. Treatment with ESP-B4 relieved AR in rats, and elevated miR-146a-5p in the EVs from the nasal epithelial cells, apparently in relation to effects on helper T cell Th1/Th2 equilibrium. ConclusionOverall, ESP-B4 can promote miR-146a-5p secretion, affect the Th1/Th2 balance of helper T cells, and relieve AR symptoms through Smad3/GATA-3 interaction, thus presenting a potential strategy for AR treatment.

Shoseiryuto Ameliorated TDI-Induced Allergic Rhinitis by Suppressing IL-33 Release from Nasal Epithelial Cells.

Toluene diisocyanate (TDI) is a major cause of occupational asthma and rhinitis. Shoseiryuto (SST) is one of the traditional herbal medicines (Kampo medicine) and has long been used as a natural medicine for allergic diseases such as allergic rhinitis (AR) and asthma. Recent studies have shown that the expression and release of IL-33, which regulates the TH2 cytokine response in epithelial cells, is an important step in developing the inflammatory response of the nasal mucosa. In this study, we investigated whether SST may ameliorate the TDI-induced AR-related symptoms in rats and inhibit IL-33 release from nasal epithelial cells. An AR rat model was generated by sensitization and induction with TDI. SST was administered during the sensitization period. AR-related symptoms in rats were evaluated, and IL-33 release was measured both in vivo and in vitro. SST suppressed symptoms appearing in TDI-induced AR model rats, such as elevated serum histamine and IL-33 levels in nasal lavage fluid (NLF)/serum, which were suppressed by SST administration. TDI-induced IL-33 release from the nasal epithelial cell nuclei was also observed and suppressed in SST-treated rats and cultured nasal epithelial cells. These results suggest that SST ameliorates the symptoms of TDI-induced AR at least partially by inhibiting IL-33 release from nasal epithelial cells.

The effect of topical intranasal H89 and dimethylsulfoxide on AQP5 levels and histopathological findings in an experimental allergic rhinitis rat model

The effect of topical intranasal H89 and dimethylsulfoxide on AQP5 levels and histopathological findings in an experimental allergic rhinitis rat model

In vivo visualization and analysis of ciliary motion in allergic rhinitis models induced by ovalbumin.

Due to the lack of an assessment approach, the image of in vivo nasal ciliary motion of allergic rhinitis (AR) has never been captured and analyzed to date. Here, we have used an optimized approach to analyze the nasal ciliary function in vivo in AR rats. The digital microscopy system, a method for direct observation of ciliary motion in a living AR rat model, was applied to visualize and measure ciliary motion in vivo, including ciliary beat frequency (CBF) and ciliary beat distance (CBD). The AR rat model was established by ovalbumin sensitization. Comparisons of nasal ciliary motion in vivo between the experimental group (ovalbumin sensitization, allergen, or histamine) and the control group were analyzed. In the living rat model of allergic rhinitis, CBF and CBD decreased to 57.8 and 73.1% of the control group, respectively, but were restored after administration of chlorpheniramine maleate. Ovalbumin (OVA) significantly inhibited the ciliary motion of normal mucosa in vivo. However, responding to the OVA challenge, the ciliary motion of OVA-sensitized mucosa would not decrease further and stay at a stable level. Histamine stimulated in vivo ciliary motion quickly within 30 min, but afterward, the ciliary motion gradually decreased below the baseline. These results have clarified that in vivo ciliary motion was impaired by nasal mucosal sensitization, and this impairment was most likely related to allergen challenge and histamine. In addition, the short-term stimulation and long-term inhibition effects of histamine on in vivo ciliary motion were first reported in this study.

Effects of rosmarinic acid on the inflammatory response in allergic rhinitis rat models after PM2.5 exposure.

BackgroundStudies have shown the promising prospects of rosmarinic acid (RosA) for the prevention and treatment of allergic diseases.ObjectiveThe aim of this study was to investigate the effects of RosA on inflammatory reaction in rat models of allergic rhinitis (AR) after PM2.5 exposure.MethodsAllergic rhinitis rat models were established by ovalbumin sensitization, and PM2.5 was applied at a concentration of 1000 μg/m3, 3 h a day for 30 consecutive days. RosA was administered via intraperitoneal injection (20 mg/kg/d) for seven consecutive days. Allergic nasal symptoms were recorded. The expressions of interleukin (IL)‐4, IL‐13, interferon (INF)‐γ, and OVA‐sIgE were determined by ELISA. Histopathological changes in nasal mucosa were observed by HE staining. mRNA expressions of T‐bet and GATA‐3 in nasal mucosa were detected by RT‐PCR. NF‐κBp65 in cell nuclei and IκBα in cytoplasm were analyzed by Western blot.ResultsPM2.5 exposure worsened allergic nasal symptoms in AR rats, while RosA ameliorated these symptoms. Histopathologically, AR rats exhibited disorganized nasal mucosal epithelium, cell exfoliation, eosinophilic infiltration of lamina propria, gland swelling, and submucosal vascular congestion, which were aggravated by PM2.5 exposure and alleviated by RosA. RosA decreased the expressions of IL‐4, IL‐13, and increased the level of IFN‐γ in PM2.5‐exposed AR rats. After RosA intervention, the expressions of GATA‐3 mRNA and NF‐κBp65 in PM2.5‐exposed AR rats were significantly reduced, while those of T‐bet mRNA and IκBα were markedly increased.ConclusionRosmarinic acid may alleviate symptoms of AR rat models exposed to PM2.5 through the modulation of the NF‐κB pathway and Th1/Th2 balance.

Protective role of lycopene in experımental allergic rhinitis in rats

ObjectiveWe investigate whether lycopene has a protective effect in an experimental rat model of allergic rhinitis. MethodsExperimental animals (65 rats) were randomized to 7 groups (Sham-Control, Lycopene 10 mg/kg/day, Lycopene 20 mg/kg/day, Intranasal lycopene drops, Intranasal steroid, Corn oil, Allergic Rhinitis). Rats were sensitized by administering of ovalbumin intraperitoneally and intranasally. In addition to ovalbumin; lycopene, corn oil and steroids were given to the relevant groups. Nasal symptom scores of the rats were recorded throughout the study. At end of the study, after intracardiac blood sample collection, all rats were sacrificed, and nasal tissues were examined histopathologically. Serum total immunoglobulin E (IgE) and ovalbumin (OVA) specific IgE were studied from all rats before and after the study. ResultsThere was a statistically significant increase (p < 0.05) in OVA specific IgE values measured before and after the study in all groups except the sham group. In serum total IgE values; there was a statistically significant increase after treatment in allergic rhinitis, corn oil, lycopene 10 mg and intranasal lycopene drops group, but other groups did not show any significant change. Histopathological study with hematoxylin-eosin staining and cyclooxygenase-2 (COX-2), matrix metalloproteinase-9 (MMP-9), vasoactive intestinal peptide (VIP) expression found that lycopene suppresses inflammation with both nasal administration and increased dose. Nasal symptom scores were observed to decrease significantly in all lycopene and steroid groups compared to allergic rihinits and corn groups. ConclusionIt was determined that lycopene were effective in the treatment of allergic rhinitis, and this effect was found to be stronger with increasing doses of lycopene.

Luteolin ameliorates inflammation and Th1/Th2 imbalance via regulating the TLR4/NF-κB pathway in allergic rhinitis rats

Objective Luteolin has an anti-allergic effect but its mechanism is not clear. This study attempted to determine the mechanisms of luteolin in rhinitis. Methods Allergic rhinitis rat model was established by ovalbumin (OVA) stimulation. Then, the rats were treated with normal saline, luteolin, or lipopolysaccharide (LPS) for 14 days. Nasal symptoms were scored; the histopathological changes of nasal mucosa were detected by hematoxylin–eosin staining. Serum levels of Th1 type cytokines (IFN-γ, IL-2), Th2 type cytokines (IL-4, IL-5, IL-13), and OVA-specific IgE (sIgE) were determined by ELISA. The expressions of Toll-like receptor 4 (TLR4) and p65 in nasal mucosa were detected by Western blot or immunohistochemistry. Results Luteolin decreased symptom scores, specifically, the scores in control group, model group, model + 0.1 mg/kg luteolin, model + 1 mg/kg luteolin, and model + 10 mg/kg luteolin groups were 0.63 ± 0.52, 7.88 ± 0.83, 1.38 ± 0.52, 2.75 ± 0.46, and 5.00 ± 0.53, respectively. Luteolin ameliorated nasal mucosa inflammation by promoting the down-regulated levels of Th1 type cytokines, and suppressing the up-regulated levels of Th2 type cytokines, OVE-sIgE, TLR4, and p65. LPS further increased symptom scores, aggravated nasal mucosa inflammation, improved the unbalance of Th1/Th2 type cytokines, and lowered the expressions of OVE-sIgE, TLR4, and p65. Moreover, LPS reversed the effect of luteolin on allergic rhinitis rats. Conclusion Luteolin ameliorated inflammation and Th1/Th2 imbalance via regulating the TLR4/NF-κB pathway in allergic rhinitis rats. This study provided novel evidence that luteolin could be used as a candidate drug in allergic rhinitis treatment.

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

Exposure to fine particulate matter (PM2.5) increases the incidence of allergic rhinitis (AR). microRNA (miRNA) can regulate cell proliferation, invasion and apoptosis. However, the mechanism of miR-338–3p in mediating PM2.5-induced autophagy in AR animal models remains unknown. To explore the mechanism of miR-338–3p in PM2.5-induced autophagy in AR, the human nasal epithelium cells and AR model exposed to PM2.5 were deployed. The results showed that miR-338–3p was down-regulated in both nasal mucosa of PM2.5-exacerbated AR rat models and PM2.5-treated RPMI-2650 cells. Forced expression of miR-338–3p could inhibit autophagy in vitro. miR-338–3p specifically bound to UBE2Q1 3′-untranslated region (3′ UTR) and negatively regulated its expression. Overexpression of UBE2Q1 attenuated the inhibitory effects of miR-338–3p on PM2.5-induced autophagy of RPMI-2650 cells through AKT/mTOR pathway. Moreover, our in vivo study found that after administration of agomiR-338–3p in AR rats model, the expression of autophagy-related proteins decreased and nasal symptoms alleviated. In conclusion, this study revealed that miR-338–3p acts as an autophagy suppressor in PM2.5-exacerbated AR by directly targeting UBE2Q1 and affecting AKT/mTOR pathway.

Allergic rhinitis impairs working memory in association with drop of hippocampal – Prefrontal coupling

Allergic rhinitis (AR) is a chronic inflammatory disease frequently associated with a deficit in learning and memory. Working memory is an important system for decision making and guidance, which depends on interactions between the ventral hippocampus (vHipp) and the prelimbic prefrontal cortex (plPFC). It is still unclear whether AR influences the activity and coupling of these brain areas, which consequently may impair working memory. The current study aimed to examine alterations of the vHipp-plPFC circuit in a rat model of AR. Our results show decreased working memory performance in AR animals, accompanied by a reduction of theta and gamma oscillations in plPFC. Also, AR reduces coherence between vHipp and plPFC in both theta and gamma frequency bands. Cross-frequency coupling analyses confirmed a reduced interaction between hippocampal theta and plPFC gamma oscillations. Granger causality analysis revealed a reduction in the causal effects of vHipp activity on plPFC oscillations and vice versa. A significant correlation was found between working memory performance with disruption of functional connectivity in AR animals. In summary, our data show that in AR, there is a deficit of functional coupling between hippocampal and prefrontal network, and suggest that this mechanism might contribute to working memory impairment in individuals with AR.

Ozone inhalation induces exacerbation of eosinophilic airway inflammation and Th2-skew immune response in a rat model of AR

BackgroundOzone (O3) exposure elicits allergic rhinitis (AR) exacerbations by mechanisms that remain poorly understood. We used a rat model to investigate the effects of O3 on eosinophilic airway inflammation and Th2-related response. MethodsSprague-Dawley (SD) rats were sensitized and challenged with ovalbumin (OVA) to make AR models. Three groups of AR rats were exposed respectively to 0.5, 1.0, 2.0 ppm of O3 for 2 h daily over 6 weeks consecutively and studied 24 h later. Normal rats exposed to O3 alone were used as controls. Nasal symptoms and OVA-specific immunoglobulin E (OVA-sIg E) in the serum were evaluated. Inflammatory cells in nasal lavage fluid (NLF) were classified and counted. Cytokines protein levels in NLF were assessed by ELISA. The pathological changes in the nasal mucosa were examined by histology. ResultsThe combination of allergen and repeated O3 exposure in rats induced a significant increase of the number of sneezes, nasal rubs, amount of nasal secretion and OVA-sIgE in the serum, accompanied by enhancement of eosinophils in NLF and nasal mucosa. The increase of interleukin-5 (IL-5), IL-13, Eotaxin and decrease of INF-γ protein levels in NLF were detected in AR rats after O3 inhalation. Hematoxylin and eosin staining showed disordered arrangement of the nasal mucosa epithelium and eosinophilic infiltration in a concentration-dependent manner. ConclusionsO3 inhalation deteriorated symptoms in AR rats, and the possible mechanism is that ozone co-exposure could enhance the expression of Th2 cytokines, eosinophilic airway inflammation dose-dependently. The observation is helpful for us to understand the synergistic effect of O3 in the air pollution and allergen on aggravating allergic rhinitis.

Effects of N-acetylcysteine on oxidative stress and inflammation reactions in a rat model of allergic rhinitis after PM2.5 exposure

Particulate matter 2.5 (PM2.5) exposure can increase the prevalence of allergic rhinitis (AR), the mechanism underlying which may include oxidative stress and inflammatory response. As a ROS quenching agent, N-acetylcysteine (NAC) can attenuate the accumulation of inflammatory cells and hyper-responsiveness in animal asthma models. To explore the effect of NAC on the oxidative stress and inflammatory reactions in AR rats exposed to PM2.5, we analyzed the components of PM2.5 and examined the nasal symptoms, redox level in nasal mucosa, Th1/Th2-related serum cytokines, nasal mucosal histopathology and ultrastructure in AR rat models with NAC intervention after PM2.5 exposure. The results showed that the high concentrations of metal cations and PAHs in PM2.5 could aggravate Th2-dominant allergic inflammation in AR model and cause redox imbalance, accompanied by nasal epithelial cell stripping and eosinophil infiltration, while NAC intervention could alleviate the clinical symptoms of AR model after PM2.5 exposure, correct the redox imbalance, reduce the Th2 cytokines, reduce eosinophil infiltration, and promote the moderate regeneration of epithelial cells. The mechanism of NAC reversing PM2.5-mediated action may be related to its anti-oxidant and anti-inflammatory effects, which may provide some new insights for the prevention of AR exacerbated by exposure to PM2.5.

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

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