Korean Red Ginseng and Ginsenoside Rg3 Suppress Asian Sand Dust-Induced Epithelial-Mesenchymal Transition in Nasal Epithelial Cells.

Chronic rhinosinusitis (CRS) is characterized by chronic inflammation of the sinonasal mucosa with epithelial dedifferentiation toward the mesenchymal phenotype, known as the epithelial-mesenchymal transition (EMT). Asian sand dust (ASD) can induce nasal mucosal inflammation and cause the development of EMT. Korean red ginseng (KRG) and ginsenoside Rg3 have been used as traditional herbal medicines to treat various diseases. The aim of this study was to investigate their effect on ASD-induced EMT in nasal epithelial cells. Primary nasal epithelial cells were incubated with ASD with or without KRG or Rg3, and the production of transforming growth factor-ß1 (TGF-ß1) and interleukin (IL)-8 was measured. EMT markers were determined by RT-PCR, Western blot analysis, and confocal microscopy, and transcription factor expression by Western blot analysis. The effect on cell migration was evaluated using the wound scratch assay. Results showed ASD-induced TGF-ß1 production, downregulation of E-cadherin, and upregulation of fibronectin in nasal epithelial cells. KRG and Rg3 suppressed TGF-ß1 production (31.7% to 43.1%), upregulated the expression of E-cadherin (26.4% to 88.3% in mRNA), and downregulated that of fibronectin (14.2% to 46.2% in mRNA and 52.3% to 70.2% in protein). In addition, they suppressed the ASD-induced phosphorylation of ERK, p38, and mTOR, as well as inhibiting the ASD-induced migration of nasal epithelial cells (25.2% to 41.5%). The results of this study demonstrate that KRG and Rg3 inhibit ASD-induced EMT by suppressing the activation of ERK, p38, and mTOR signaling pathways in nasal epithelial cells.

Effect of Korean Red Ginseng and Rg3 on Asian Sand Dust-Induced MUC5AC, MUC5B, and MUC8 Expression in Bronchial Epithelial Cells.

Korean Red ginseng (KRG), commonly used in traditional medicine, has anti-inflammatory, anti- oxidative, and anti-tumorigenic properties. Asian sand dust (ASD) is known to aggravate upper and lower airway inflammatory responses. BEAS-2B cells were exposed to ASD with or without KRG or ginsenoside Rg3. Mucin 5AC (MUC5AC), MUC5B, and MUC8 mRNA and protein expression levels were determined using quantitative RT-PCR and enzyme-linked immunosorbent assay. Nuclear factor kappa B (NF-κB), activator protein 1, and mitogen-activated protein kinase expression and activity were determined using western blot analysis. ASD induced MUC5AC, MUC5B, and MUC8 mRNA and protein expression in BEAS-2B cells, which was significantly inhibited by KRG and Rg3. Although ASD-induced mucin expression was associated with NF-κB and p38 mitogen-activated protein kinase (MAPK) activity, KRG and Rg3 significantly suppressed only ASD-induced NF-κB expression and activity. KRG and Rg3 inhibited ASD-induced mucin gene expression and protein production from bronchial epithelial cells. These results suggest that KRG and Rg3 have potential for treating mucus-producing airway inflammatory diseases.

Immunomodulative Effects of Chamaecyparis obtusa Essential Oil in Mouse Model of Allergic Rhinitis.

The present study aims to investigate the immunomodulatory effects of essential oil from Chamaecyparis obtusa (EOCO) in an ovalbumin (OVA)-induced allergic rhinitis (AR) mouse model. BALB/c mice were intraperitoneally sensitized and stimulated with OVA. From day 22 to 35, 0.01% and 0.1% ECOC was intranasally administered 1 h before OVA stimulation. Nasal symptoms, as well as serum total and OVA-specific immunoglobulin (Ig) E levels, were measured. Interleukin (IL)-4, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels in nasal lavage fluid (NLF) and their production by activated splenocytes were measured. Histological changes in the sinonasal mucosa were evaluated through hematoxylin and eosin and periodic acid-Schiff staining procedure. Th cytokines and their transcription factor mRNA expressions were determined using reverse-transcription polymerase chain reaction. Intranasal EOCO administration significantly suppressed allergic symptoms, OVA-specific IgE level, sinonasal mucosal inflammatory cell infiltration, and mucus-producing periodic acid-Schiff (PAS) positive cell count. EOCO also significantly inhibited IL-4, IL-10, and TNF-α levels in NLF and activated splenocytes. Th2 and Treg related cytokines and their transcription factors in sinonasal mucosa were significantly suppressed through intransal EOCO instillation. In conclusion, repetitive EOCO intranasal instillation showed anti-inflammatory and anti-allergic effects by suppressing nasal symptoms and inhibiting the production and expression of inflammatory mediators in the OVA-induced AR mouse model.

Anti-inflammatory effect of bee venom in an allergic chronic rhinosinusitis mouse model.

Bee venom (BV) has long been used as anti-inflammatory agent in traditional oriental medicine; however, the effect of BV on chronic rhinosinusitis (CRS) is not commonly studied. The aim of the present study was to determine the anti-inflammatory effect of BV on an allergic CRS mouse model. An allergic CRS mouse model was established following the administration of ovalbumin with Staphylococcus aureus enterotoxin B (SEB) into the nose. A total of 0.5 or 5 ng/ml of BV were intranasally applied 3 times a week for 8 weeks. Histopathological alterations were observed using hematoxylin and eosin, and Periodic acid Schiff staining. The levels of inflammatory cell infiltration, interleukin (IL)­4, IL­10 and interferon (INF)­Î³ in nasal lavage fluid (NLF) were measured. Nuclear factor (NF)­κB and activator protein (AP)­1 expressions were also determined by immunohistochemical staining. The group treated with BV had significantly decreased inflammatory cell infiltration and PAS­positive cells. The levels of INF­Î³, and neutrophil and eosinophil counts in NLF were significantly decreased, and the SEB­induced NF­κB and AP­1 expressions in mouse nasal mucosa were significantly suppressed by 0.5 and 5 ng/ml BV. Thus, BV exerted significant anti­inflammatory effects in an allergic CRS mouse model and may have potential value for the treatment of CRS.

Bee venom at different concentrations modulates the aeroallergen-induced activation of nasal polyp epithelial cells.

Bee venom (BV) has long been used as an oriental traditional medicine for the control of pain and inflammation. However, BV's anti-inflammatory mechanisms remain unclear. This study aimed to clarify the potential clinical efficacy of BV concerning the anti-inflammatory effect on nasal epithelial cell inflammation. Nasal polyp epithelial cells were obtained from patients. Cells were exposed to Alternaria alternata, Aspergillus nigra, Dermatophagoides pteronyssinus, Dermatophagoides farina and lipopolysaccharide with or without various concentrations of BV. Interleukin (IL)-6, IL-8, and granulocyte macrophage colony-stimulating factor were measured to determine the activation of epithelial cells. Nuclear factor-ĸB (NF-ĸB) and activator protein 1 expression and activity were determined with Western blot analysis and ELISA. Cytotoxicity of BV was measured using a CellTiter-96® aqueous cell proliferation assay kit. Cell survival was significantly decreased at BV concentrations exceeding 5 µg/ml. Fungi-induced cytokine production was more effectively inhibited by BV than house dust mite. Alternaria enhanced NF-ĸB expression, which was strongly inhibited by BV. BV appears to be relatively safe, and is of potential value for the treatment of airway inflammation and/or immunologic diseases.

Effects of topical amphotericin B on expression of cytokines in nasal polyps.

OBJECTIVE: Although chronic rhinosinusitis (CRS) is one of the most frequently reported chronic diseases its etiology is not well understood. Recently, fungi have been proposed to influence the chronicity of rhinosinusitis. If fungi do play an important role then topical antifungal treatment may improve the inflammatory process of CRS. Therefore, in this study we measured inflammatory cytokine levels in nasal polyps after intranasal antifungal irrigation. MATERIAL AND METHODS: Nasal polyps were collected before and 4 weeks after treatment with 100 mg/l topical amphotericin B (n = 16), 50 mg/l topical amphotericin B (n = 14) or normal saline (n = 11). The cytokine--IL-5, IL-8, interferon-gamma, RANTES--protein content of polyp homogenates were determined by means of ELISA. RESULTS: Nasal polyps were found to contain large amounts of cytokines (IL-5, IL-8 and RANTES) compared with normal inferior turbinates. After 4 weeks of treatment with topical agents, IL-5 levels tended to decrease in comparison with those of the other cytokines, but this difference was not statistically significant. CONCLUSIONS: Topical amphotericin B treatment and nasal saline irrigation both influence the expression of nasal polyp cytokines. Topical nasal irrigation may influence the inflammatory process of CRS.