Desmoglein 3 gene mediates epidermal growth factor/epidermal growth factor receptor signaling pathway involved in inflammatory response and immune function of anaphylactic rhinitis

• Published in: Biomedicine & pharmacotherapy 2019-10, Vol.118, p.109214-109214, Article 109214
• Main Authors: Ri, Han, Peiyan, Zheng, Jianqi, Wang, Yunteng, Zhao, Gang, Li, Baoqing, Sun
• Format: Article
• Language: English
• Subjects: Anaphylactic rhinitis; Anaphylaxis - genetics; Anaphylaxis - immunology; Anaphylaxis - metabolism; Animals; Desmoglein 3; Desmoglein 3 - genetics; Disease Models, Animal; Epidermal Growth Factor - genetics; Epidermal Growth Factor - metabolism; Epidermal growth factor/epidermal growth factor receptor signaling pathway; ErbB Receptors - genetics; ErbB Receptors - metabolism; Gene Expression Regulation; Immune function; Inflammation; Mice, Inbred BALB C; Nasal Mucosa - immunology; Nasal Mucosa - metabolism; Nasal mucosal inflammation; Rhinitis, Allergic - genetics; Rhinitis, Allergic - immunology; Rhinitis, Allergic - metabolism; Signal Transduction
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2019.109214

[Display omitted] •DSG3 gene silencing can inhibit the activation of EGFR/EGF signaling pathway.•DSG3 gene silencing alleviates inflammation of anaphylactic rhinitis nasal mucosa.•DSG3 gene silencing enhances the immune adherence function of red blood cells.•DSG3 gene is expected to be important target for anaphylactic rhinitis treatment. To investigate the effects of desmoglein 3 (DSG3) gene mediating epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) signaling pathway on inflammatory response and immune function of anaphylactic rhinitis (AR). Ten of the seventy male BALB/c mice were randomly selected as the normal control group, and the remaining 60 were used to construct the AR mice model. AR model mice were divided into 6 groups: model group (instilled with 5 μL saline), empty vector group (instilled with 5 μL of liposome and empty vector mixture), siRNA-DSG3 group (instilled with 5 μL of liposome and siRNA-DSG3 carrier mixture), AG1478 group (instilled with 5 μL of EGF/EGFR inhibitor AG1478), siRNA-DSG3+AG1478 group (instilled with 5 μL of liposome and siRNA-DSG3 carrier and EGF/EGFR inhibitor AG1478 mixture) and oe-DSG3 group, 10 in each group. After taking serum, each group of mice was sacrificed to get nasal mucosa tissues. HE staining was used to observe the pathological changes of nasal mucosa tissues in each group. The expression levels of DSG3, EGF and EGFR in nasal mucosa tissues of mice in each group were detected by qRT-PCR and western blot methods respectively. TUNEL staining was used to observe the apoptosis of nasal mucosa cells in mice. The expression of IgE, INF-γ, TNF-α, IL-2, IL-4 and IL-6 in serum of mice was determined by ELISA method. The immune adhesion function of red blood cells was detected by complement sensitization yeast hemagglutination method. All the mice with AR showed different degrees of nasal mucosa injury and inflammatory cell infiltration, and silencing DSG3 or inhibiting the activity of EGF signaling pathway could alleviate the nasal mucosa injury. Compared with control group, the INF-γ and IL-2 levels of serum in AR model mice were significantly decreased; IgE, TNF-α, IL-4 and IL-6 levels were significantly increased (all P