Mucosa Of Allergic Rhinitis Rats Research Articles

Investigation of Expression and Correlation of Exogenous Interleukin-10 and GATA Binding Protein-3 in Nasal Mucosa of Allergic Rhinitis Rats

Investigation of Expression and Correlation of Exogenous Interleukin-10 and GATA Binding Protein-3 in Nasal Mucosa of Allergic Rhinitis Rats

Combined Treatment With H1 and H4 Receptor Antagonists Improves Th2 Inflammatory Responses in the Nasal Mucosa of Allergic Rhinitis Rats.

Histamine H1 receptor (H1R) antagonists are the first-line drugs for the treatment of allergic rhinitis (AR) at present. Emerging evidence supports an important role of histamine H4 receptor (H4R) in allergic diseases. However, information regarding the effects of combined treatment with H1 and H4 receptor antagonists in AR is limited. We aimed to assess the effects of combined treatment with H1R and H4R antagonists on Th2 inflammatory responses in the nasal mucosa of AR rats. Sprague Dawley rats were sensitized with ovalbumin and treated with H1R antagonist desloratadine or/and H4R antagonist JNJ7777120. Western blotting was used to assay the phenotypic markers of mature dendritic cells in the nasal mucosa, including major histocompatibility complex class II (MHC-II) and co-stimulatory molecules CD80, CD86 and OX40 ligand (OX40L). Th2 inflammatory cytokines including interleukin-4, 5 and 13 in nasal lavage fluids were determined by using enzyme-linked immunoassay. The treatment with desloratadine alone down-regulated the CD86 expression, and decreased the production of Th2 cytokines, but had no impact on the expression of MHC-II, CD80 and OX40L. The administration of NJ7777120 alone reduced the levels of CD86, OX40L and Th2 cytokines, whereas MHC-II and CD80 expression was unaffected. The combination of desloratadine and JNJ7777120 showed more significant synergistic therapeutic effects than monotherapy. H4R antagonist acted synergistically with H1R antagonist to reduce Th2 inflammatory responses by down-regulating CD86 and OX40L expression in the nasal mucosa of AR rats. The combination with H1R and H4R antagonists might be a new strategy for AR treatment.

Astragalus Polysaccharides Attenuate Ovalbumin-Induced Allergic Rhinitis in Rats by Inhibiting NLRP3 Inflammasome Activation and NOD2-Mediated NF-κB Activation.

Allergic rhinitis (AR) is an IgE-mediated chronic inflammatory disease of the allergic nasal mucosa. It has a significant effect on quality life; most patients with AR also suffer from sleep disorders, mood disorders, and deterioration in social relationships. As increasing numbers of medicinal plants show productive anti-inflammatory activity against inflammatory diseases, there is growing interest in natural medicinal plant ingredients. To this end, we selected Astragalus polysaccharides (APS) to evaluate its anti-inflammatory effect on ovalbumin-induced AR rats, and we further explored its impact on NLRP3 inflammasome activation and NOD2-mediated NF-κB activation. We found that APS can alleviate the nasal symptom of AR rats and attenuate pathological alterations. APS also reduced the inflammatory cytokine levels. APS not only inhibited the NLRP3 inflammasome activation but also inhibited NF-κB activation by decreasing NOD2 expression and blocking the phosphorylation of NF-κB (p65). In conclusion, APS can effectively improve the inflammatory symptoms of nasal mucosa in AR rats, which may be mediated by the inhibition of NLRP3 inflammasome activation and NOD2-mediated NF-κB activation. These findings indicate that APS has the potential to be used as a therapeutic agent for AR.

Effects of sIL-13Rα2 on the nasal mucosa goblet cell apoptosis of allergic rhinitis of rats

Objective: To investigate the effects of sIL-13Rα2 on the apoptosis of goblet cell in nasal mucosa of allergic rhinitis rats. Methods: Forty healthy male Wistar rats were randomly divided into 4 groups (10 rats per group): control group (group A), AR group (group B), sIL-13Rα2 group (group C) and triamcinolone acetonide group (group D). Ovalbumin (OVA) and aluminum hydroxide were used to establish the AR rat model. After the establishment of AR rat models, 50 μl PBS, 100 μg/50 μl IL-13Rα2 and 3.5 μg/50 μl triamcinolone acetonide were respectively dropped into each nasal cavity of every rat two times a week from 4 to 10 week in group B, group C and group D. Group A was operated with saline instead of OVA. The nasal mucosa tissues were collected at 24 h after the final administration. AB-PAS staining method was used to detect the quantity and secretion of goblet cells in the nasal mucosa tissue of all groups. Immunohistochemistry method was used to detect the expression of Bax proteins.Apoptosis was detected by TUNEL method.ANOVA analysis was used to compare multiple groups, and LSD-t test was used to compare the two groups.Pearson correlation analysis was used to analyze the correlation between the Bax positive cell rate of goblet cells and the rate of apoptotic cells. The difference was statistically significant with P<0.05. Results: Compared with group A, there were more goblet cells and hypersecretion of mucus in the nasal mucosa tissue of rats in group B while fewer in group C. The goblet cells in group C and group D were significantly fewer than that in group B (0.639 00±0.831 vs 0.956 7±0.980, 0.661 90±0.657 vs 0.956 7±0.980, t value was 2.748, 2.767, respectively, all P<0.05). The immunohistochemistry results showed that the positive expression rates of Bax protein in goblet cells of group C and group D were significantly higher than that in group B (0.880 2±0.125 vs 0.568 7±0.953, 0.938 4±0.200 vs 0.568 7±0.953, t value was -2.292, -2.685, respectively, all P<0.05). The apoptosis rates of goblet cell in nasal mucosa of group C and group D were also significantly higher than that in group B (0.516 0±0.079 vs 0.274 0±0.056, 0.535 4±0.829 vs 0.274 0±0.056, t value was -17.671, -2.225, respectively, all P<0.05). The expression of Bax protein and apoptosis of goblet cells were positively correlated (r=0.859, P<0.01). Conclusion: sIL-13Rα2 can induce apoptosis of the goblet cells in nasal mucosa of allergic rhinitis rats, by inhibiting IL-13 and up regulating Bax.

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.

Mesenchymal stromal cells ameliorate acute allergic rhinitis in rats.

Mesenchymal stromal cells (MSCs) have been extensively investigated as a potential antiinflammatory treatment in many inflammatory‐related diseases; however, it remains unclear whether MSCs could be used to treat acute allergic rhinitis. A rat model of allergic rhinitis was treated with MSCs. The effect of MSCs on the inflammation of allergic rhinitis was evaluated by sneezing, nose rubbing, the pathology of the nasal mucosa, and the expression of interleukin 4, tumour necrosis factor alpha, and immunoglobulin E in the serum of rats. Also, the population of MSCs isolated from umbilical cords of humans was evaluated to determine if they could inhibit the symptoms and inflammation of acute allergic rhinitis in a rat model. We observed that this population of cells inhibited sneezing, nose rubbing, and changes in the pathology of the nasal mucosa. Intriguingly, we observed that MSCs reduced the expression of interleukin 4, tumour necrosis factor alpha, and immunoglobulin E in the serum. Furthermore, MSCs reduced the expression of histamine and the recruitment of macrophages in the nasal mucosa of allergic rhinitis rats. We reasoned that the effect of MSCs on allergic rhinitis might be through its regulation of the secretion of related cytokines from macrophages during the process of acute allergic rhinitis. This work suggested that MSCs from the umbilical cords of humans could be used as a positive clinical therapy for the human disease.

Effects of inhibiting the phosphorylation of JNK by absorbed INF-γon the remodeling of nasal mucosa in allergic rhinitis rats

Objective:To study the role of phosphorylated JNK(c-Jun N-terminal kinase) on nasal mucosa remodeling in allergic rhinitis(AR) rats and the influence of IFN-γon IL-1β,JNK and nasal mucosa remodeling.Method:According to random number table,48 Wistar rats were divided into control group(A group),AR group(B group),IFN-γgroup(C group) and triamcinolone acetonide group(D group).The rats in group B,C and D were sensitized and provocated for inducing AR by intraperitoneal injection of ovalbumin(OVA) and Al(OH)₃.Thirty minutes before intranasally challenged,rats in three groups were administrated by instillation of PBS,IFN-γand triamcinolone acetonide into nasal cavities,while the group A rats were administrated by saline solution.Ten rats in each group were selected to enter the final experiment.The density of IL-1βin serum and nasal lavage fluid were tested by ELISA.The mean absorbance (mA) of phosphorylated JNK and c-Jun were tested by immunohistochemistry.Western Blot detected the P-JNK level in nasal tissue homogenate.Result:The density of IL-1βin serum and nasal lavage fluid in group C and group D were significantly lower than that of group B (P<0.01).Immunohistochemistry study showed that the protein expression level of phosphorylated JNK and c-Jun of nasal mucosa were significantly increased in group B,but significantly reduced in group C and group D .The mA of phosphorylated JNK and c-Jun in group B were significantly higher than those in the group C and group D(P<0.01).The Western blot showed that the P-JNK of nasal tissue homogenate in group B was higher than that of group C and group D (P<0.01).Conclusion: The phosphorylation of JNK played an important role in nasal mucosa remodeling.IFN-γcould inhibit the phosphorylation of JNK and reduce the nasal mucosa remodeling.The mechanisms may be achieved through down-regulation of IL-1β.

Mucin 5 Subtype AC Expression and Upregulation in the Nasal Mucosa of Allergic Rhinitis Rats

To elucidate the functions of nuclear factor kappa B (NF-κB) in mucin hypersecretion in allergic rhinitis (AR), we examined the in vivo effects of an NF-κB inhibitor, ammonium pyrrolidine dithiocarbamate (PDTC), on mucin 5 subtype AC (MUC5AC) expression in the nasal mucosa of ovalbumin-sensitized rats. Randomized animal study. Academic medical center. Sprague Dawley rats were randomized into a control group (group A), an AR model group (group B), and an AR model treated with an NF-κB inhibitor (group C). Rats in groups B and C were sensitized systemically and locally by ovalbumin injection and inhalation, whereas group A was treated with normal saline in place of ovalbumin. Pyrrolidine dithiocarbamate (100 mg/kg/d) was given to group C by intraperitoneal injection for 5 days. NF-κBp65, MUC5AC, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were detected by immunohistochemistry, Western blotting, enzyme-linked immunosorbent assay, or real-time polymerase chain reaction. NF-κB was activated in group B, and significant NF-κBp65 protein was expressed in the nucleus of cells from the nasal mucosa, resulting in upregulated transcription from TNF-α and IL-6 genes, as well as increased contents of TNF-α and IL-6 in the nasal lavage fluids. Pyrrolidine dithiocarbamate inhibited nuclear localization of NF-κBp65 and subsequent downregulation of the transcription and secretion of TNF-α and IL-6. MUC5AC was upregulated in group B but reduced in a time-dependent manner after inhibition of NF-κB activation. NF-κB activation might induce MUC5AC hypersecretion in AR rats by inflammatory cytokines TNF-α and IL-6.

Effects of glucocorticoid on calcium-activated chloride channel expression in nasal mucosa in allergic rhinitis rats

To investigate the expression of CLCA3 and Muc5ac in nasal mucosa in allergic rhinitis rats and the effects of glucocorticoid on its expression. Thirty SD rats were randomly divided into allergic rhinitis group, dexamethasone group and control group. Expression of CLCA3 mRNA and Muc5ac protein in nasal mucosa were detected by RT-PCR and immunohistochemical assay, respectively. CLCA3 mRNA and Muc5ac protein in allergic rhinitis group were significantly higher than those in control group (t = 8.565, 5.317, P < 0.01, respectively). The increased expression of CLCA3 mRNA in allergic rhinitis group was well correlated with the expression of Muc5ac protein and the correlation coefficient was 0.813 (P < 0.05). After treatment with dexamethasone, the expression of CLCA3 mRNA and Muc5ac protein was notably lower than that in allergic rhinitis group (t = 3.102, 2.226, P < 0.05, respectively). The stronger gene expression of CLCA3 exists, complicated with mucus overproduction in the nasal mucosa of allergic rhinitis rats. CLCA3 expression may play a pivotal role in mucus overproduction in allergic rhinitis. Dexamethasone substantially downregulates the expression of CLCA3 mRNA and Muc5ac protein.