Nasal Mucosa In Allergic Rhinitis Research Articles

Bimin Kang ameliorates the minimal persistent inflammation in allergic rhinitis by reducing BCL11B expression and regulating ILC2 plasticity

Ethnopharmacological relevanceMinimal persistent inflammation (MPI) is a major contributor to the recurrence of allergic rhinitis (AR). The traditional Chinese herbal medicine known as Bimin Kang Mixture (BMK) have been used in clinics for decades to treat AR, which can relieve AR symptoms, reduce inflammatory response and improve immune function. However, its mechanism in controlling MPI is still unclear. Aim of the studyThis study aims to assess the therapeutic effect of BMK on MPI, and elaborate the mechanism involved in BMK intervention in BCL11B regulation of type 2 innate lymphoid cell (ILC2) plasticity in the treatment of MPI. Material and methodsThe effect of BMK (9.1 ml/kg) and Loratadine (15.15 mg/kg) on MPI was evaluated based on symptoms, pathological staining, and ELISA assays. RT-qPCR and flow cytometry were also employed to assess the expression of BCL11B, IL-12/IL-12Rβ2, and IL-18/IL-18Rα signaling pathways associated with ILC2 plasticity in the airway tissues of MPI mice following BMK intervention. ResultsBMK restored the airway epithelial barrier, and markedly reduced inflammatory cells (eosinophils, neutrophils) infiltration (P < 0.01) and goblet cells hyperplasia (P < 0.05). BCL11B expression positively correlated with the ILC2 proportion in the lungs and nasal mucosa of AR and MPI mice (P < 0.01). BMK downregulated BCL11B expression (P < 0.05) and reduced the proportion of ILC2, ILC3 and ILC3-like ILC2 subsets (P < 0.05). Moreover, BMK promoted the conversion of ILC2 into an ILC1-like phenotype through IL-12/IL-12Rβ2 and IL-18/IL-18Rα signaling pathways in MPI mice. ConclusionBy downregulating BCL11B expression, BMK regulates ILC2 plasticity and decreases the proportion of ILC2, ILC3, and ILC3-like ILC2 subsets, promoting the conversion of ILC2 to ILC1, thus restoring balance of ILC subsets in airway tissues and control MPI.

Acupoint injection ameliorates Th1/Th2 imbalance through Toll-like receptor 4/activator protein-1 signal pathway and improves inflammatory response in rats with allergic rhinitis

To observe the effect of acupoint injection on serum T helper (Th)1/Th2 related cytokines, and the expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and activator protein-1 (AP-1) of nasal mucosa in allergic rhinitis (AR) rats, so as to explore its mechanism underlying improvement of AR. Thirty-two SD rats were randomly divided into normal, model, non-acupoint injection and acupoint injection groups (n=8 in each group). The AR model was established by ovalbumin sensitization. In the acupoint injection group, "Yintang" (GV24+) and bilateral "Yingxiang" (LI20) were selected for injection of mixture solution of dexamethasone and lidocaine (0.05 mL/acupoint), once every 4 days for a total of 4 times. The non-acupoints, located at the midpoint between the "Houhai" and "Huantiao" (GB30) on the bilateral hips and the sites 5 cm inferior to the axillary were injected with the same dose of mixture solution as that in the acupoint injection group. The AR severity was assessed by cumulative quantification scoring methods (including the numbers of nose-catching and sneezes, and the amount of nasal secretions in 30 min). The pathological changes of nasal mucosa were observed by HE staining. The contents of immunoglobulin E (IgE), interleukin (IL)-4 and interferon (IFN)-γ in serum were detected by ELISA. The expressions of TLR4 and MyD88 in nasal mucosa was detected by immunofluorescence. The expression of AP-1 in nasal mucosa was detected by Western blot. Following modeling, the AR symptom score, serum IgE and IL-4 contents and expression of TLR4, MyD88 and AP-1 of nasal mucosa were significantly increased in the model group than those in the normal group (P<0.01), while the serum IFN-γ content was significantly decreased (P<0.01). Compared with the model group and non-acupoint injection group, the AR symptom score, the serum contents of IgE and IL-4 and the expressions of TLR4, MyD88 and AP-1 in nasal mucosa were significantly decreased in the acupoint injection group (P<0.01, P<0.05), while the serum IFN-γ content was significantly increased (P<0.01). H.E. staining of the nasal mucosa showed that most of the epithelium fell off, the lamina propria vessels expanded, the glands proliferated, and eosinophils and lymphocytes infiltrated in the model and non-acupoint injection groups, and those were significantly improved in the acupoint injection group. Acupoint injection can effectively improve allergic inflammation of the nose in AR rats, which may be related with its function in inhibiting the abnormal activation of TLR4/AP-1 signaling pathway and regulating the imbalance of Th1/Th2.

Involvements of Nrf2 and oxidative stress in the ozone-elicited exacerbation in an allergic rhinitis model

Objective and designAn experimental rat allergic rhinitis(AR) model was made to explore the effect of different concentrations of ozone exposure and evaluate the roles of nuclear factor erythroid 2-related factor 2(Nrf2) and oxidative stress in ozone exposure. MethodSprague-Dawley rats were sensitized with ovalbumin (OVA). Three groups of AR rats were exposed respectively to different concentrations of ozone for 2 h on 6 weeks. Nasal symptoms and OVA- specific Ig E in the serum were evaluated. The pathological changes in the nasal mucosa were examined. Malondialdehyde (MDA) level and activity of superoxide dismutase(SOD) and glutathione peroxidase (GSH-Px,GPX) in the nasal mucosa tissue were measured through a spectrophotometry-based method. Nrf2、Kelch-1ike ECH- associated protein-l (Keap1) proteins was measured by western blotting. GPX1、GPX2 mRNA were detected by quantitative real time-PCR(qRT-PCR). ResultsOur results showed that ozone exposure induced a significant increase of the number of sneezes, nasal rubs, amount of nasal secretion and OVA-sIgE in the serum of AR model. Ozone effected oxidative stress in different concentration. The content of MDA in AREH group was significantly higher than AR groups. The activities of SOD and GSH-Px in nasal mucosa showed different trends in different concentration groups. The activities of SOD and GSH-Px in AREL and AREM groups were higher than AR group, but decreased at AREH group. The nucleoprotein level of Nrf2 in AREL and AREM groups was higher than AR groups. However, in AREH group, it was significantly decreased, compared with AREL and AREM groups. GPX1 and GPX2 mRNA levels in nasal mucosa showed the same trend in different exposure groups. ConclusionsDifferent concentrations of ozone inhalation causes changes of the expression of Nrf2 nuclear protein and its target genes in nasal mucosa of AR. High concentration ozone breaks the redox balance and aggravates oxidative damage in AR. This study suggests that inhibiting oxidative stress might be a solution for ozone-elicited detrimental effects on AR.

MiR-124-3p relieves allergic rhinitis by inhibiting dipeptidyl peptidase-4

MicroRNA-124-3p (miR-124-3p) and dipeptidyl peptidase-4 (DPP4) are closely related to the development of inflammation. Allergic rhinitis (AR) models in mice and HNEpC cells were established. AR progression was assessed assessing by the frequency of nasal rubbing and sneezing, hematoxylin and eosin (HE), and TUNEL staining. Tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), granulocyte–macrophage colony-stimulating factor (GM-CSF), eotaxin, and MUC5AC were assessed by enzyme-linked immunosorbent assay and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Apoptosis in HNEpC cells was assessed using flow cytometry. DPP4, activated-caspase-3, and pro-caspase-3 protein expression were evaluated by western blotting. In addition, we clarified the influence of miR-124-3p-targeted DPP4 on AR inflammation and cell injury. MiR-124-3p was downregulated in AR nasal mucosa tissue. Upregulation of miR-124-3p reduced the frequency of nasal rubbing and sneezing, pathological changes, eosinophil number, and apoptosis of nasal mucosa, TNF-α and IL-6 protein and mRNA levels in serum and HNEpC cells, and MUC5AC, eotaxin, and GM-CSF levels in HNEpC cells. Downregulation of miR-124-3p has the opposite effect. Therefore, the miR-124-3p /DPP4 axis may be an attractive target for AR therapy.

Twist1 sustains the apoptosis resistance in eosinophils in nasal mucosa of allergic rhinitis

Eosinophils (Eos) are the canonical effector cells in allergic rhinitis (AR) and many inflammatory diseases. The mechanism of eosinophilia occurring in the lesion sites is not fully understood yet. Twist1 protein (Twist, in short) is an apoptosis inhibitor that also has immune regulatory functions. This study aims to investigate the role of Twist in the pathogenesis of eosinophilia in AR. In this study, surgically removed human nasal mucosal samples were obtained from patients with chronic sinusitis and nasal polyps with AR (the AR group) or without AR (the nAR group). Eos were isolated from the samples by flow cytometry. We found that abundant Eos were obtained from the surgically removed nasal mucosa tissues of both nAR and AR groups. Significantly higher Ras activation was detected in AR Eos than that in nAR Eos. Ras activation was associated with the apoptosis resistance in AR Eos. The Twist (an apoptosis inhibitor) expression was higher in AR Eos, which was positively correlated with the Ras activation status. The sensitization to IgG induced Twist expression in Eos, in which Ras activated the MAPK-HIF-1α pathway, the latter promoted the Twist gene transcription. Twist bound Rac GTPase activating protein-1 to sustain the Ras activation in Eos. Ras activation sustained the apoptosis resistance in Eos. In conclusion, high Ras activation was detected in the AR nasal mucosal tissue-isolated Eos. IgG-sensitization induced Ras activation and Twist expression in Eos, that conferred Eos the apoptosis resistance.

Downregulation of miR-96-5p Inhibits mTOR/NF-κb Signaling Pathway via DEPTOR in Allergic Rhinitis

Background: This study aims to investigate the regulatory effect of microRNA-96-5p (miR-96-5p) in the pathophysiological process of allergic rhinitis (AR). Methods: Nasal mucosal tissue samples were collected from AR patients and healthy controls. An in vitro AR model was established by stimulating human nasal epithelial cells (HNECs) with interleukin (IL)-13. The expressions of target genes and proteins were measured by qPCR, Western blot, or ELISA. Dual-luciferase reporter assay and pull-down assay were performed to confirm the interaction between miR-96-5p and DEP domain-containing mammalian target of rapamycin-interacting protein (DEPTOR). Results: The level of miR-96-5p was increased while the expression of DEPTOR was decreased in AR patients. The expressions of proinflammatory cytokines were markedly increased and the mammalian target of rapamycin (mTOR)/NF-κB pathway was activated in HNECs following IL-13 stimulation. miR-96-5p downregulation alleviated the stimulated function by IL-13. DEPTOR was the target of miR-96-5p. Knockdown of DEPTOR reversed the function of miR-96-5p inhibitor on IL-13-stimulated HNECs. Conclusions: The current study showed that miR-96-5p and DEPTOR were aberrantly expressed in AR nasal mucosa. miR-96-5p knockdown inhibited the production of inflammatory cytokines and the activation of mTOR/NF-κB pathway via targeting DEPTOR. These findings suggested that miR-96-5p might be used as a diagnostic marker and therapeutic target for the treatment of AR.

Effects of narrow-band UVB on nasal symptom and upregulation of histamine H1 receptor mRNA in allergic rhinitis model rats.

BackgroundPhototherapy with narrow‐band ultraviolet B (narrow‐band UVB) is clinically effective treatment for atopic dermatitis. In the present study, we examined the effects of intranasal irradiation with narrow‐band UVB on nasal symptom, upregulation of histamine H1 receptor (H1R) gene expression and induction of DNA damage in the nasal mucosa of allergic rhinitis (AR) model rat.MethodsAR model rats were intranasally irradiated with 310 nm of narrow‐band UVB. Nasal mucosal levels of H1R mRNA were measured using real‐time quantitative reverse transcriptase (RT)‐PCR. DNA damage was evaluated using cyclobutane pyrimidine dimer (CPD) immunostaining.ResultsIn toluene 2,4‐diisocyanate (TDI)‐sensitized rats, TDI provoked sneezes and H1R gene expression in the nasal mucosa. Intranasal pre‐irradiation with 310 nm narrow‐band UVB at doses of 600 and 1400, but not 200 mJ/cm2 significantly inhibited the number of sneezes and upregulation of H1R gene expression provoked by TDI. CPD‐positive cells appeared in the nasal mucosa after intranasal narrow‐band UVB irradiation at a dose of 1400, but not 200 and 600 mJ/cm2. The suppression of TDI‐provoked sneezes and upregulation of H1R gene expression lasted 24 hours, but not 48 hours, after narrow‐band UVB irradiation with a dose of 600 mJ/cm2.ConclusionsIntranasal pre‐irradiation with narrow‐band UVB dose‐dependently inhibited sneezes and upregulation of H1R gene expression of the nasal mucosa in AR model rats, suggesting that the inhibition of nasal upregulation of H1R gene expression suppressed nasal symptom. The suppression after narrow‐band UVB irradiation at a dose of 600 mJ/cm2 was reversible without induction of DNA damage. These findings indicated that low‐dose narrow‐band UVB phototherapy could be effectively and safely used for AR treatment in a clinical setting.Level of EvidenceNA.

Влияние экспрессии гена интерлейкина-33 на клинико-морфологические характеристики слизистой оболочки носа при аллергическом рините

Влияние экспрессии гена интерлейкина-33 на клинико-морфологические характеристики слизистой оболочки носа при аллергическом рините

DMBT1 has a protective effect on allergic rhinitis

ObjectiveDeleted in malignant brain tumors 1 (DMBT1) is a secreted scavenger receptor cysteine-rich (SRCR) protein, predominantly expressed in nasal mucosal epithelial cells. In previous experiments, we found large amounts of DMBT1 present in the nasal cavity mucosa of allergic rhinitis (AR) patients. However, the exact role of DMBT1 in AR remains unclear. This study is to investigate the mechanism through which DMBT1 exerts its effects on AR progression. MethodDMBT1 levels in the nasal lavage (NL) fluid and the nasal mucosa in AR and control groups were determined by ELISA and IHC. Next, mice were sensitized with ovalbumin; intranasal administrations of recombinant DMBT1 were then performed. DMBT1 in the nasal mucosa of mice were determined by IHC and WB. Nasal symptoms were estimated. IL-4 and IL-5 in BAL fluid and eosinophils infiltration in the nasal cavity were measured through ELISA and HE staining, respectively. ResultsDMBT1 levels were found to be significantly higher in the NL fluid and nasal mucosa of AR patients and AR mice, compared to control groups (p < 0.01). Levels of IL-4 and IL-5 in BAL and infiltration of eosinophils into the nasal mucosa were significantly increased in AR mice, compared to control mice (p < 0.01). rDMBT1 significantly reduced the number of nasal sneezing and rubbings in AR mice (p < 0.01). It also inhibited the eosinophil infiltration in the nasal mucosa and significantly decreased the production of IL-4 and IL-5 in BAL (p < 0.01). ConclusionThis study demonstrated that rDMBT1 alleviates AR progression in mice via inhibiting IL-4 and IL-5 production and eosinophils infiltration in the nasal cavity.

MiR-146a mimic attenuates murine allergic rhinitis by downregulating TLR4/TRAF6/NF-κB pathway.

Aim: This study aims to investigate whether microRNA (miR)-146a exerts therapeutic potential to allergic rhinitis (AR). Methods: Female BALB/c mice were randomly divided into the AR and miR-146a groups. miR-146a was administered into the nostril before ovalbumin (OVA) challenge daily on days 21-28. Results: The expression level of miR-146a in AR nasal mucosa was significantly decreased. miR-146a mimic markedly attenuated sneezing and nasal rubbing events, decreased the levels of ovalbumin-specific IgE as well as mastocyte- and basophil-related inflammatory cytokines, reduced inflammatory cells, affected the T-helper 2-released cytokines. Furthermore, miR-146a mimic inhibited the expressions of proteins relevant to Toll-like receptor 4 (TLR4)/TRAF6/NF-κB signaling pathway. Conclusion: The anti-inflammatory effects of miR-146a on AR might exert through the inhibition of the toll-like receptor 4 (TLR4)/TRAF6/NF-κB signaling pathway to some extent.

The effect of NK-1R-siRNA on expression of inflammatory factors in allergic rhinitis

Objective: To explore the effect of neurokinin-1 receptor small interfering RNA (NK-1R-siRNA) on the expression of inflammation factors in allergic rhinitis (AR). Methods: Twenty-four male SD rats were divided into three groups randomly (by random number table methord): NK-1R-siRNA group, negative control siRNA (NC-siRNA) group and saline group, with 8 rats in each group. SD rats were sensitized and challenged with ovalbumin (OVA) to induce AR. The rats were treated intranasally with NK-1R-siRNA, NC-siRNA or saline before and during the challenge period. The AR symptoms were observed. The levels of OVA-specific IgE were measured by enzyme-linked immunosorbent assay (ELISA). The levels of NK-1R expression in the nasal mucosal tissues were determined by real time PCR (RT-PCR) and immunohistochemistry. Antibody array was used in studying the expression of inflammation cell factors in nasal mucosa. SPSS 11.0 software was used for one-factor analysis of variance. Results: Compared with saline group, AR symptoms relived significantly in NK-1R-siRNA group (nose rubbing (31.4±8.9)/15 min vs (69.5±17.9)/15 min, sneezing (7.2±1.9)/15 min vs (23.7±9.2)/15 min, nasal secretions (7.1±2.3) mg vs (24.1±4.4) mg, t value was 38.100, 17.125, 16.837, respectively, all P<0.01), and the level of serum OVA-specific IgE was also reduced ((8.56±0.73) ng/ml vs (18.05±1.22) ng/ml, t=9.787, P<0.01). The RT-PCR and immunohistochemistry results showed that the expression of NK-1R in nasal mucosa of NK-1R-siRNA group was remarkably reduced than that of the NC-siRNA group and saline group. After the treatment of NK-1R-siRNA, the expression of interleukin (IL) 1α, IL-1β, IL-4, IL-6 and IL-13 decreased, while the interferon-γ (IFN-γ) and IL-10 increased. Conclusion: NK-1R-siRNA could regulate the release of inflammation factors in AR nasal mucosa, thus relive the allergic inflammation.

Expression of LC3 and ECP in allergic rhinitis and their significance

Objective:To investigate the expression of microtubuleassociated protein 1 light chain 3 beta(LC3) and eosinophil cationic protein in allergic rhinitis(AR) for further understanding of the pathogenesis of AR. Method: Twenty cases of normal nasal mucosa and 20 cases of AR nasal mucosa were collected. Histological changes of nasal mucosa were examined by hematoxylin and eosin(HE) staining. The expression of LC3 and ECP were measured by immunohistochemistry(IHC) and Western Blot(WB). Result: The tissue samples demonstrated a large number of eosinophils and lymphocytes infiltration in AR. IHC revealed that LC3 and ECP expression were higher in AR than in normal nasal mucosa(P<0.05). WB also showed that the relative expression levels of protein expression of LC3 and ECP were greater in AR than in controls. The expression level of LC3 was positively correlated with that of ECP protein in AR. Conclusion: LC3 and ECP were upregulated and positively correlated in AR, indicating that autophagy plays an important role in the toxicity of allergic rhinitis , which provides theoretical basis for the precise treatment of AR.

Effect of RORC inhibitor on HIF-1α and VEGF in nasal mucosa of allergic rhinitis of mice

Objective: To investigate the effects of the retinoic acid receptor related orphan C (RORC) inhibitor (SR1001) on the expression changes of proteins of hypoxia induced factor (HIF-1α) and vascular endothelial growth factor (VEGF) in the nasal mucosa of mice with allergic rhinitis (AR) model. Methods: Thirty BALB/c were randomly divided into normal group, AR model group and RORC inhibitor group, 10 mice each group. AR model of mice was established by ovalbumin (OVA) sensitization method. RORC inhibitor group was given intraperitoneal injection of SR1001 (25 mg/kg), while AR model group intraperitoneal injection of the same volume of 0.9% normal saline. The symptom score of the mice was determined every weekend after administration. The pathological morphological changes in the nasal mucosa tissue obtained from anesthetized mice were observed by light microscope. The expression of HIF-1α and VEGF protein were detected by immunohistochemistry. IFN-γ, IL-17, and sIgE in the serum were detected by ELISA and the expression of HIF-1α and VEGF in the nasal mucosal tissue of the mice were measured by Western blot. One-way ANOVA was used for inter-group comparison. LSD method was used for inter-group comparison with equal variance, and Dunnett T3 method for inter-group comparison with unequal variance. P<0.05 was considered statistically significant. Results: The AR model was successfully established. Compared with the model group, the RORC inhibitor group significantly reduced the symptom score of AR mice (4.02±0.97 vs 8.50±1.76, t=7.050, P<0.01). The damaged mucosal epithelium appeared to be improved, the glands and dilated ducts tended to be normal, the mast goblet cells significantly reduced, and the infiltration of inflammatory cells in the inherent mucosa reduced. Meanwhile, the content of IL-17 and sIgE in serum decreased [(25.10±4.11) ng/ml vs (42.56±5.98) ng/ml, (0.875±0.244) ng/ml vs (1.982±0.365) ng/ml, t value was 14.141, 10.275, respectively, all P<0.01] and the content of IFN-γ increased [(61.32±8.83) pg/ml vs (38.94±5.97) pg/ml, t=8.133, P<0.01]. The expression of HIF-1α and VEGF protein in the nasal mucosal tissues of AR mice significantly reduced (0.92±0.08 vs 1.67±0.31, 1.12±0.21 vs 2.54±0.46, t value was 7.408, 8.880, respectively, all P<0.01). Conclusion: The RORC inhibitor has the therapeutic effect on AR by changing the content of inflammatory factors in AR mice and reducing the expression level of HIF-1α and VEGF in the nasal mucosa.

Expression and significance of Notch1-Jagged1 in allergic rhinitis

Objective: To study the expression and significance of Notch1-Jagged1 in nasal mucosa of allergic rhinitis (AR) mouse model in various stages and in the serum of AR patients. Methods: Thirty-six mice were divided into 3 groups: control group, basal sensitization group (OVA) and OVA/AR group, with 12 mice in each group. Allergic symptom in each group were scored after AR model establishment. HE staining method was used to observe the nasal mucosa eosinophils infiltration. ELISA was used to detect the serum level of total IgE. Flow cytometry was used to detect the change of Treg cells in each group. Western blot was used to detect the expression of Notch1 and Jagged1 in nasal mucosa. Flow cytometric bead array (CBA) was used to detect the level of Th1/Th2/Th17 cytokines in splenic lymphocytes. The serum was obtained from 50 patients with AR and 30 control volunteers in Department of Otorhinolaryngology Head and Neck Surgery, Renmin Hospital of Wuhan University from June to October 2017. ELISA was used to detect the expression of Notch1 and Jagged1. Results: Compared with the control group, the allergy symptom, the number of nasal mucosal eosinophils and the level of total IgE were not significantly different in basal sensitization group, but increased significantly in OVA/AR group (6.11±0.78 vs 0.67±0.50, 77.67±5.61 vs 10.33±0.82, (106.80±11.91) pg/ml vs (82.45±19.80) pg/ml, t value was 19.471, 34.848, 2.542, respectively, all P<0.05). Compared with the control group, the ratio of Treg cell increased in basal sensitization group but decreased in OVA/AR group ((10.29±0.47)% vs (9.28±0.16)%, (8.49±0.15)% vs (9.28±0.16)%, t value was 5.838, 4.540, respectively, all P<0.01). Compared with control group, the expression of Notch1 increased significantly both in basal sensitization group and OVA/AR group (1.04±0.05 vs 0.71±0.05, 1.83±0.10 vs 0.71±0.05, t value was 9.293, 31.363, respectively, all P<0.01); and the expression of Jagged1 only increased significantly in OVA/AR group (0.41±0.04 vs 0.21±0.01, t=13.472, P<0.01). It was found that Notch1 was positively correlated with the level of IL-6, IL-10 by Pearson test (r value was 0.98, 0.87, respectively, all P<0.01). Compared with control volunteers, the expression of Notch1 and Jagged1 increased significantly in AR group patients ((1 135.0±254.9) pg/ml vs (436.0±139.3) pg/ml, (1 200.2±401.0) pg/ml vs (559.9±124.2) pg/ml, t value was 13.99, 11.94, respectively, all P<0.01). Conclusions: The expression of Notch1 receptor and ligand increased significantly in the pathogenesis of AR. Notch1-Jagged1 may promote the occurrence and development of AR by up-regulating the expression of IL-6 and IL-10.

Clara cell protein 16 release from the nasal mucosa in allergic rhinitis, chronic rhinosinusitis, and exposure to air pollutants.

Clara cell protein 16 (CC16) is a small protein mainly produced by non-ciliated Clara cells in the respiratory epithelium. It has an anti-inflammatory role in chronic upper and lower airway eosinophilic inflammations. Decreased levels of CC16 are found in the nasal secretions and plasma of patients with chronic eosinophilic inflammatory disorders, such as asthma, allergic rhinitis, and chronic rhinosinusitis with or without nasal polyps, as well as in people exposed to high levels of air pollutants. Intranasal corticosteroid administration suppresses chronic inflammation of the nasal mucosa driven by eosinophils and stimulates local CC16 production. CC16 can be a reliable biomarker of the beneficial effects of perennial allergic rhinitis and chronic rhinosinusitis therapy and of the functional recovery of the nasal mucosa after treatment with topical glucocorticoids.

Acupoint Injection at "Yingxiang"(LI 20) and "Yintang"(GV 29) May Relieve Nasal Allergic Symptoms Possibly by Down-regulating Expression of Histamine Receptor H 1 and H 4 in Nasal Mucosa of Allergic Rhinitis Rats

To observe the effect of acupoint injection at "Yingxiang"(LI 20) and "Yintang"(GV 29) on nasal allergic reactions and the expression of histamine receptor H 1 and H 4 in nasal mucosa of allergic rhinitis (AR) rats, so as to reveal its mechanism underlying improvement of AR. SD rats were randomized into normal, model, non-acupoint injection and acupoint injection groups (n=8 in each). The AR model was established by intraperitoneal (i.p.) injection of mixture of ovalbumin, aluminium hydroxide gel and normal saline (once every other day, for 7 times), and nasal drip of ovalbumin (on the following day of i.p.for 7 days). The mixture solution of lidocaine, dexamethasone (DXM) and transfer factor (0.1 mL/acupoint or non-acupoint) was injected into bilateral LI 20 and GV 29 in the acupoint injection group, or into the non-acupoints (about 5 cm below the armpit on both sides, and the middle point between the left "Houhai"[GV 1] and "Huantiao"[GB 30]), on the 1st , 5th, 9th, and 13th day after modeling. Symptoms of sneezing, nasal discharge, nose-rubbing, etc. were scored after the treatment. The expression levels of H1 R and H4 R proteins and genes in the nasal mucosa tissue were determined using immunohistochemistry and quantitative real-time PCR, respectively. Compared with the normal group, the symptom score and the expression levels of H1 R, H4 R proteins and genes in nasal mucosa were significantly increased in the model group (P<0.05). After acupoint injection for 4 times, the symptom score and the expression levels of H1 R, H4 R proteins and mRNAs were significantly down-regulated in the acupoint injection group relevant to the model group (P<0.05). There were no significant differences between the non-acupoint and the model groups in the abovementioned indexes (P>0.05), suggesting a specificity of the effect of acupoint injection. Acupoint injection can relieve the allergic symptoms of AR rats, which may be related to its effects in down-regulating the over expression of H1 R and H4 R proteins and genes in the nasal mucosa.

A hypothesis of the Effect of a New Nasal Spray Made from Natural Medicines on Allergic Rhinitis in Animals

To verify the effect of a new nasal spray made from natural medicines on allergic rhinitis in animals. Methods: The main natural medicines contained in Acusine nasal spray plus essential traditional Chinese medicine contained in drugs for allergic rhinitis in Chinese market were used. By preparation process of extraction of traditional Chinese medicine such as steam distillation, ethanol extraction, a new nasal spray made from natural medicines was prepared. In the meantime, 24 BALB/c mice and New Zealand white rabbits were used. Then, mice were randomly divided into four group; control group, beclomethasone dipropionate group, Acusine group and new spray group, 6 mice in each group. Moreover, the effect of the new nasal spray made on passive cutaneous anaphylaxis was conducted by detecting absorptions of Evan’s blue (620nm) in the four groups. Allergic rhinitis models in 40 New Zealand white rabbits were established. Consequently, 40 allergic rhinitis models in rabbits were randomly divided into control group, Acusine group and new spray group, 10 rabbits in each group. The four groups were sprayed nasally with saline, Acusine spray and new spray respectively, three times/d, for 30 days. The nasal resistances in the four groups were measured with a rhinoresistometer. Moreover, their nasal mucosa was taken for HE staining. Consequently, their pathological manifestations were observed. The results: Absorption of Evan’s blue (620nm) of new spray group will be found significantly lower than Acusine group (P<0.05) and will have no significantly difference compared with beclomethasone dipropionate group(P>0.05). On the other hand, absorption of Evan’s blue (620nm) of beclomethasone dipropionate group will be significantly lower than Acusine group (P<0.05). Moreover, The nasal resistances of new spray group will be significantly lower than Acusine group (P<0.05) and will have no significantly difference compared with beclomethasone dipropionate group (P».05). Moreover, the nasal resistances of beclomethasone dipropionate group will be significantly lower than Acusine group (P<0.05). While, the nasal mucosa of control group will be found typical as nasal mucosa of allergic rhinitis. However, the nasal mucosa of beclomethasone dipropionate group, Acusine group and new spray group will be better than control group. Of them, new spray group will be the best. The nasal mucosa of beclomethasone dipropionate group will show the manifestation of drug-induced rhinitis. The conclusion: The invented new spray will not only have a better treatment effect on allergic rhinitis, similar with beclomethasone dipropionate, than Acusine Nasal Spray but also will not leave side effect on nasal mucosa, compared with beclomethasone dipropionate. Thus, the new spray made from natural medicines can be further studied as a better prescription drug, rather than an OTC like Acusine Nasal Spray, to replace beclomethasone dipropionate nasal spray. However, further study that would be required to produce a more meaningful answer.

Novel approach to assessing the effects of sulphurous thermal waters on an in vitro 3D nasal integrity model from allergic rhinitis patients

Background Chronic allergic rhinitis is associated with inflammation of the nasal mucosa, changes in nasal epithelial integrity and subsequent clinical symptoms. Sulfurous (natural mineral) thermal waters (STWs) have been used as complementary therapeutic approach to chronic rhinitis / rhinosinusitis, with studies demonstrating clinical efficacy, namely in terms of improvement in mucociliary clearance time, nasal resistance and nasal flow. However, very few data exist regarding the effects of STW-based treatment on nasal epithelial integrity parameters. We have hypothesized that STWs treatment will modulate an amelioration of general integrity of allergic rhinitis nasal mucosa.

Histopathological effects of intranasal phototherapy and nasal corticosteroids in allergic rhinitis in a rabbit model

Allergic rhinitis is one of the most common health problems and has a major effect on quality of life. Although new-generation antihistamines and nasal steroids are the main treatment options, complete resolution cannot be obtained in some patients. Besides common side effects such as nasal irritation and epistaxis, the use of these drugs is controversial in some patients, such as pregnant or breastfeeding women. These findings highlight the need for new treatment options. Although phototherapy has been successfully used in the treatment of atopic dermatitis, which is an IgE-mediated disease and shares several common pathogenic features with allergic rhinitis, there are limited studies about its role in the treatment of allergic rhinitis. In this study, we aimed to evaluate and compare the histopathological effects of intranasal phototherapy (Rhinolight) and nasal corticosteroid treatment on the nasal mucosa in allergic rhinitis in a rabbit model and we found that both treatment options significantly reduced inflammation in the nasal mucosa without increasing apoptosis of mucosal cells.

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.