scholarly journals Therapeutic effects of SKF-96365 on murine allergic rhinitis induced by OVA

2021 ◽  
Vol 35 ◽  
pp. 205873842110150
Author(s):  
Guangyi Ba ◽  
Ru Tang ◽  
Xiwen Sun ◽  
Zhipeng Li ◽  
Hai Lin ◽  
...  

Introduction: SKF-96365 is regarded as an inhibitor of receptor-mediated calcium ion (Ca2+) entry. The current study aimed to explore the effects of SKF-96365 on murine allergic rhinitis (AR). Methods: Intranasal SKF-96365 administration was performed on OVA induced murine AR. Serum and nasal lavage fluid (NLF) from mice were harvested to assay IgE and inflammatory cytokines using ELISA method. Inflammatory cells were counted and analyzed in NLF. Nasal mucosa tissues were collected from mice and used for HE staining, immunohistochemistry (IHC) staining, and real-time PCR detection. Results: SKF-96365 had therapeutic effects on murine AR manifesting attenuation of sneezing, nasal rubbing, IgE, inflammatory cytokines, inflammatory cells, TRPC6 immunolabeling, and TRPC6, STIM1 and Orai1 mRNA levels in AR mice. Conclusion: SKF-96365 could effectively alleviate the symptoms of murine AR. SKF-96365 could suppress TRPC6, STIM1, and Orai1 activities, leading to the downregulation of inflammatory cytokines and inflammatory cells in murine AR.

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 1202-1212
Author(s):  
Aichun Zhang ◽  
Yangzi Jin

AbstractAllergic rhinitis (AR) is one of the most common chronic diseases. This study examined whether microRNA (miR)-182-5p plays a role in AR by regulating toll-like receptor 4 (TLR4). First, data demonstrated that TLR4 was a target of miR-182-5p. Subsequently, AR mouse model was established to explore the role of miR-182-5p and TLR4 in AR in vivo. Initially, quantitative reverse transcription-PCR (qRT-PCR) analysis indicated that miR-182-5p was downregulated, while TLR4 expression was upregulated in AR mice. Then we found that miR-182-5p mimic reduced the frequency of sneezing and nose rubbing of the AR mice. In addition, miR-182-5p mimic significantly increased ovalbumin (OVA)-specific IgE and leukotriene C4 expression levels in nasal lavage fluid (NLF) and serum of AR mice. miR-182-5p mimic decreased the number of inflammatory cells in NLF of AR mice. It also reduced the levels of inflammatory factors in the serum of AR mice, such as interleukin (IL)-4, IL-5, IL-13, IL-17 and tumor necrosis factor (TNF)-α, while increasing the release of IFN-γ and IL-2. Finally, miR-182-5p mimic inhibited NF-κB signaling pathway activation in AR mice. However, all effects of miR-182-5p mimic on AR mice were reversed by TLR4-plasmid. In conclusion, miR-182-5p/TLR4 axis may represent a novel therapeutic target for AR.


2019 ◽  
Vol 33 (4) ◽  
pp. 420-432
Author(s):  
Zhong Bing ◽  
Du Jin-Tao ◽  
Liu Feng ◽  
Luo Ba ◽  
Liu Ya-Feng ◽  
...  

Background Astragalus membranaceus (AM), a traditional Chinese medicine, has been used to treat allergic diseases, but the mechanism for treating allergic rhinitis (AR) remains unclear. Objective The purpose of this study was to look at the anti-inflammatory effect of AM on AR and the mechanism of anti-allergy. Methods The mouse model of AR was induced by ovalbumin. Allergic symptoms, number of eosinophils in nasal mucosa, and levels of inflammatory cells in nasal lavage fluid were analyzed. We explored the serum immunoglobulin E (IgE), interleukin-4 (IL-4), IL-5, IL-13, interferon-γ (IFN-γ), and IL-10. Besides, the relative mRNA of IL-4, IL-5, and IL-13 was also detected in nasal mucosa tissue. The proportion of CD4+ CD25+ Foxp3+ T cells in the spleen and nasal lymphoid tissue were analyzed. The mRNA levels of nuclear factor-kappa B p65 (NF-κB p65) and inhibitory kappa B alpha (IκBα), as well as NF-κB p65 DNA binding activity, were tested. We also measured the protein levels of NF-κB p65 and p-NF-κB p65 in nasal mucosa. Results AM could reduce the number of eosinophils in the nasal mucosa and decrease the levels of inflammatory cells in nasal lavage fluid. The serum IgE, IL-4, IL-5, and IL-13 were also decreased, while levels of IFN-γ and IL-10 were increased. The relative mRNA of IL-4, IL-5, and IL-13 was decreased by AM. AM increased the proportion of CD4+ CD25+ Foxp3+ T cells in the spleen and nasal lymphoid tissue. In addition, AM could reduce the activity of NF-kB by inhibiting the mRNA expression and DNA binding activity of NF-κB p65. However, AM had no significant effect on mRNA of IκBα. Above all, AM could reduce the p-NF-κB p65 protein expression of nasal mucosa. Conclusions AM could reduce the secretion of inflammatory cytokines by increasing the level of CD4+ CD25+ Foxp3+ T cells and inhibiting the activation of the NF-κB.


Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 239
Author(s):  
Peiting Li ◽  
Miranda Sin-Man Tsang ◽  
Lea Ling-Yu Kan ◽  
Tianheng Hou ◽  
Sharon Sze-Man Hon ◽  
...  

Allergic rhinitis (AR) is a highly prevalent allergic disease induced by immunoglobulin (Ig) E-mediated hypersensitivity reaction at the nasal epithelium against inhaled allergens. Previous studies have demonstrated that Pentaherbs formula (PHF), a modified herbal formula comprising five herbal medicines (Flos Lonicerae, Herba Menthae, Cortex Phellodendri, Cortex Moutan and Rhizoma Atractylodis), could suppress various immune effector cells to exert anti-inflammatory and anti-allergic effects in allergic asthma and atopic dermatitis. The present study aimed to further determine the anti-inflammatory activities of PHF in an ovalbumin (OVA)-induced AR BALB/c mouse model. Nasal symptoms such as sneezing and nose rubbing were recorded and the serum total IgE and OVA-specific IgG1, as well as interleukin (IL)-4, IL-5, IL-10, IL-13, chemokines CXCL9 CXCL10, and tumor necrosis factor (TNF)-α concentrations in nasal lavage fluid (NALF) were measured during different treatments. Effects of PHF on the expression of inflammatory mediators in the sinonasal mucosa were quantified using real-time QPCR. PHF was found to suppress allergic symptoms, infiltration of inflammatory cells, and hyperplasia of goblet cells in the nasal epithelium of the OVA-induced AR mice. PHF could reduce OVA-specific IgG1 level in serum, and TNF-α and IL-10 in nasal lavage fluid (NALF), significantly up-regulate the splenic regulatory T (Treg) cell level, increase the Type 1 helper T cell (Th1)/Type 2 helper T cell (Th2) ratio, and reduce the Th17 cells (all p < 0.05). PHF could also alleviate in situ inflammation in sinonasal mucosa of OVA-induced AR mice. In conclusion, oral treatment of PHF showed immuno-modulatory activities in the OVA-induced AR mice by regulating the splenic T cell population to suppress the nasal allergy symptoms and modulating inflammatory mediators, implicating that PHF could be a therapeutic strategy for allergic rhinitis.


2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Bin Lin ◽  
Bijuan Cai ◽  
Huige Wang

Abstract Honeysuckle has antiviral, antioxidative and anti-inflammatory properties. Allergic rhinitis (AR) is induced by immunoglobulin E (IgE)-mediated inflammatory reaction. Our study investigates whether honeysuckle extract (HE) has therapeutic effect on AR. An AR model of mice was established by ovalbumin (OVA). Hematoxylin–Eosin staining was used to assess nasal mucosa damage. Enzyme-linked immunosorbent assay (ELISA) was performed to determine serum histamine, IgE and interleukin (IL)-2, IL-4, IL-17 and interferon-γ (IFN-γ) from nasal lavage fluid. Western blot was carried out to analyze the protein level from nasal mucosa tissue. We found that HE not only decreased nasal rubbing and sneezing in AR mice, but also reduced AR-induced damage to nasal mucosa. Moreover, HE lowered the levels of serum IgE and histamine and inhibited IL-4 and IL-17 levels from AR mice but raised IL-2 and IFN-γ levels in AR-induced nasal lavage fluid. Our results also showed that HE elevated the protein levels of forkhead box P3 (Foxp3) and T-box transcription factor (T-bet) in AR-induced nasal mucosa tissue, whereas it inhibited signal transducer and activator of transcription (STAT) 3 and GATA binding protein 3 (GATA-3) protein levels. By regulating AR-induced inflammatory reaction and autoimmune response, HE also relieved OVA-induced AR. Thus, HE could be used as a potential drug to treat AR.


2007 ◽  
Vol 292 (2) ◽  
pp. L577-L584 ◽  
Author(s):  
Carol Lang ◽  
Chiara Murgia ◽  
Mary Leong ◽  
Lor-Wai Tan ◽  
Giuditta Perozzi ◽  
...  

There is clinical evidence linking asthma with the trace element, zinc (Zn). Using a mouse model of allergic inflammation, we have previously shown that labile Zn decreases in inflamed airway epithelium (Truong-Tran AQ, Ruffin RE, Foster PS, Koskinen AM, Coyle P, Philcox JC, Rofe AM, Zalewski PD. Am J Respir Cell Mol Biol 27: 286–296, 2002). Moreover, mild nutritional Zn deficiency worsens lung function. Recently, a number of proteins belonging to the Solute Carrier Family 39 (ZIP) and Solute Carrier Family 30 (ZnT) have been identified that bind Zn and regulate Zn homeostasis. Mice were sensitized, and subsequently aerochallenged, with ovalbumin to induce acute and chronic airway inflammation. Mice received 0, 54, or 100 μg of Zn intraperitoneally. Tissues were analyzed for Zn content and histopathology. Inflammatory cells were counted in bronchoalveolar lavage fluid. Cytokine and Zn transporter mRNA levels were determined by cDNA gene array and/or real-time PCR. Zn supplementation decreased bronchoalveolar lavage fluid eosinophils by 40 and 80%, and lymphocytes by 55 and 66%, in the acute and chronic models, respectively. Alterations in Zn transporter expression were observed during acute inflammation, including increases in ZIP1 and ZIP14 and decreases in ZIP4 and ZnT4. Zn supplementation normalized ZIP1 and ZIP14, but it did not affect mRNA levels of cytokines or their receptors. Our results indicate that inflammation-induced alterations in Zn transporter gene expression are directed toward increasing Zn uptake. Increases in Zn uptake may be needed to counteract the local loss of Zn in the airway and to meet an increased demand for Zn-dependent proteins. The reduction of inflammatory cells by Zn in the airways provides support for Zn supplementation trials in human asthmatic individuals.


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