RESUMEN
Aspergillus fumigatus is commonly found in the airway and is associated with airway inflammatory diseases. Zinc oxide (ZO) is known to be an essential microelement that facilitates fungal survival, growth, and proliferation. This study aimed to investigate the impact of ZO on A. fumigatus-induced fungal sinusitis in rabbits. Twenty-eight New Zealand white rabbits were divided into four groups for this study. Group 1 (6 sides) was treated with intramaxillary phosphate buffer saline (PBS) served as the negative control, Group 2 (6 sides) received intramaxillary PBS and ZO, Group 3 (8 sides) was treated with intramaxillary A. fumigatus alone, and Group 4 (8 sides) treated with intramaxillary A. fumigatus with ZO. After 4 and 12 weeks, sinus mucosal cytokine and transcription factor expressions were determined. A histological analysis was performed to determine inflammatory cell infiltration, number of secretory cells, and mucosal thickness. Fungal biofilm formation was determined using confocal laser microscopy. The intramaxillary instillation of A. fumigatus conidia led to an increase in protein and mRNA expression of interleukin (IL)-1ß and IL-8 in the maxillary sinus mucosa. They were associated with mitogen-activated protein kinase and activator protein-1. Furthermore, intramaxillary instillation of fungal conidia resulted in significant enhancement of inflammatory cell infiltration, epithelial thickening, and fungal biofilm formation. However, intramaxillary ZO did not have a significant impact on A. fumigatus-induced cytokine protein and mRNA expression, and inflammatory cell infiltration and epithelial thickness in sinonasal mucosa. While intramaxillary instillation of A. fumigatus increased mucosal inflammation, cytokine production, and biofilm formation, the intramaxillary application of ZO did not have a significant influence on inflammation in the maxillary sinus mucosa.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias del Seno Maxilar , Humanos , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Neoplasias del Seno Maxilar/patología , Neoplasias del Seno Maxilar/diagnóstico por imagen , Neoplasias del Seno Maxilar/cirugía , Masculino , Tomografía Computarizada por Rayos X , Colesteatoma/cirugía , Colesteatoma/patología , Colesteatoma/diagnóstico por imagen , Persona de Mediana Edad , FemeninoRESUMEN
Chronic rhinosinusitis (CRS) is characterized by inflammatory cell infiltration in the sinonasal mucosa. Eosinophil and neutrophil extracellular traps (EETs and NETs, respectively) are prominently found in CRS. This study aimed to investigate the effect of airborne fungi, Alternaria alternata and Aspergillus fumigatus, on EET and NET formation. Nasal epithelial cells, eosinophils, and neutrophils were isolated from eosinophilic CRS (ECRS), non-ECRS (NECRS), and healthy control. We determined eosinophil and neutrophil transepithelial migration after fungal treatment. We then determined the release of EETs and NETs by fungi using Sytox Green staining and determined the role of reactive oxygen species (ROS) using ROS inhibitors. We identified more abundant EETs and NETs in ECRS than in NECRS. A. alternata and A. fumigatus enhanced eosinophil and neutrophil transepithelial migration. A. fumigatus strongly induced EET and NET formation in CRS and, simultaneously, suppressed fungal metabolic activity. EET formation in CRS is associated with nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase and NET formation with NADPH-oxidase and mitochondrial ROS. A. fumigatus, but not A. alternata, induced EET and NET formation, and peripheral blood eosinophils and neutrophils exhibited different immune responses against A. fumigatus following the inflammatory status of the host. Aspergillus-fumigatus-induced EET and NET formation plays a crucial role in CRS pathogenesis.
Asunto(s)
Trampas Extracelulares , Rinosinusitis , Sinusitis , Humanos , Neutrófilos/metabolismo , Trampas Extracelulares/metabolismo , Eosinófilos , Especies Reactivas de Oxígeno/metabolismo , NADP/metabolismo , Enfermedad Crónica , Sinusitis/metabolismo , Aspergillus , Aspergillus fumigatus , NADPH Oxidasas/metabolismoRESUMEN
Lidocaine, a local anesthetic, is known to possess anti-inflammatory properties. However, its clinical use is limited by inconveniences, such as its local synesthetic effects. This study evaluated lidocaine analogs designed and synthesized to overcome the disadvantages of lidocaine, having anti-inflammatory properties. Interleukin 5 (IL-5)-induced eosinophil activation and survival were evaluated using 36 lidocaine analogs with modified lidocaine structure on the aromatic or the acyl moiety or both. Eosinophil survival was evaluated using a CellTiter 96® aqueous cell proliferation assay kit. Superoxide production was determined using the superoxide dismutase-inhibitable reduction of cytochrome C method. Eosinophil cationic protein (ECP), IL-8, and transcription factor expression were determined using enzyme-linked immunosorbent assay. The platelet-activating factor (PAF)-induced migration assay was performed using a Transwell insert system. Compounds EI137 and EI341 inhibited IL-5-induced eosinophil survival and superoxide and ECP production in a concentration-dependent manner. These compounds also significantly reduced IL-8 production. Although compounds EI137 and EI341 significantly reduced phosphorylated ERK 1/2 expression, they did not influence other total and phosphorylated transcription factors. Moreover, 1000 µM of compound EI341 only inhibited PAF-induced migration of eosinophils. Lidocaine analogs EI137 and EI341 inhibited IL-5-mediated activation and survival of eosinophils. These compounds could be new therapeutic agents to treat eosinophilic inflammatory diseases.
Asunto(s)
Eosinófilos , Superóxidos , Superóxidos/metabolismo , Lidocaína/farmacología , Interleucina-5/metabolismo , Interleucina-5/farmacología , Interleucina-8/metabolismo , Factor de Activación Plaquetaria/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/metabolismoRESUMEN
Airborne fungi are ubiquitous in the environment and are commonly associated with airway inflammatory diseases. The innate immune defense system eliminates most inhaled fungi. However, some influence the development of chronic rhinosinusitis. Fungal CRS is thought of as not a common disease, and its incidence increases over time. Fungi are present in CRS patients and in healthy sinonasal mucosa. Although the immunological mechanisms have not been entirely explained, CRS patients may exhibit different immune responses than healthy people against airborne fungi. Fungi can induce Th1 and Th2 immune responses. In CRS, Th2-related immune responses against fungi are associated with pattern recognition receptors in nasal epithelial cells, the production of inflammatory cytokines and chemokines from nasal epithelial cells, and interaction with innate type 2 cells, lymphocytes, and inflammatory cells. Fungi also interact with neutrophils and eosinophils and induce neutrophil extracellular traps (NETs) and eosinophil extracellular traps (EETs). NETs and EETs are associated with antifungal properties and aggravation of chronic inflammation in CRS by releasing intracellular granule proteins. Fungal and bacterial biofilms are commonly found in CRS and may support chronic and recalcitrant CRS infection. The fungal-bacterial interaction in the sinonasal mucosa could affect the survival and virulence of fungi and bacteria and host immune responses. The interaction between the mycobiome and microbiome may also influence the host immune response, impacting local inflammation and chronicity. Although the exact immunopathologic role of fungi in the pathogenesis of CRS is not completely understood, they contribute to the development of sinonasal inflammatory responses in CRS.
Asunto(s)
Rinitis , Sinusitis , Humanos , Rinitis/patología , Sinusitis/patología , Mucosa Nasal/metabolismo , Inflamación/metabolismo , Hongos , Enfermedad CrónicaRESUMEN
Fibrous dysplasia (FD) is a rare benign disease that replaces a normal bone with abnormal fibrous and weak osseous tissue. It is usually detected in childhood and rarely occurs in old age. Although the disease is known to be caused by a genetic mutation, only a single case of FD secondary to surgery is reported in the literature. We report a case of monostotic FD of the maxillary sinus in a 70-year-old Asian woman who presented with incidental calcific lesion in the maxillary sinus on a brain computed tomography scan. At 32 months prior to presentation, the patient had undergone an endoscopic sinus surgery for a fungal ball of the same sinus. The lesion was removed by endoscopic surgery, and the histopathological evidence was consistent with FD. To the best of our knowledge, this is the second case of a postsurgical craniofacial FD, and a rare case that occurred in old age.
RESUMEN
Chronic rhinosinusitis (CRS) is a diverse chronic inflammatory disease of the sinonasal mucosa. CRS manifests itself in a variety of clinical and immunologic patterns. The histological hallmark of eosinophilic CRS (ECRS) is eosinophil infiltration. ECRS is associated with severe disease severity, increased comorbidity, and a higher recurrence rate, as well as thick mucus production. Eosinophils play an important role in these ECRS clinical characteristics. Eosinophils are multipotential effector cells that contribute to host defense against nonphagocytable pathogens, as well as allergic and nonallergic inflammatory diseases. Eosinophils interact with Staphylococcus aureus, Staphylococcal enterotoxin B, and fungi, all of which were found in the tissue of CRS patients. These interactions activate Th2 immune responses in the sinonasal mucosa and exacerbate local inflammation. Activated eosinophils were discovered not only in the tissue but also in the sinonasal cavity secretion. Eosinophil extracellular traps (EETs) are extracellular microbes trapping and killing structures found in the secretions of CRS patients with intact granule protein and filamentous chromatic structures. At the same time, EET has a negative effect by causing an epithelial barrier defect. Eosinophils also influence the local tissue microenvironment by exchanging signals with other immune cells and structural cells. As a result, eosinophils are multifaceted leukocytes that contribute to various physiologic and pathologic processes of the upper respiratory mucosal immune system. The goal of this review is to summarize recent research on the immunopathologic properties and immunologic role of eosinophils in CRS.
Asunto(s)
Pólipos Nasales , Rinitis , Sinusitis , Humanos , Eosinófilos , Pólipos Nasales/metabolismo , Sinusitis/complicaciones , Recuento de Leucocitos , Enfermedad CrónicaRESUMEN
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.
Asunto(s)
Transición Epitelial-Mesenquimal , Panax , Cadherinas/metabolismo , Movimiento Celular , Polvo , Células Epiteliales , Fibronectinas/metabolismo , Ginsenósidos , Humanos , Inflamación/metabolismo , Panax/metabolismo , ARN Mensajero/metabolismo , Arena , Serina-Treonina Quinasas TOR/metabolismo , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
BACKGROUND: Asian sand dust (ASD) and Aspergillus fumigatus are known risk factors for airway mucosal inflammatory diseases. Bacterial and fungal biofilms commonly coexist in chronic rhinosinusitis and fungus balls. We evaluated the effects of ASD on the development of A. fumigatus biofilm formation on nasal epithelial cells. METHODS: Primary nasal epithelial cells were cultured with A. fumigatus conidia with or without ASD for 72 h. The production of interleukin (IL)-6, IL-8, and transforming growth factor (TGF)-ß1 from nasal epithelial cells was determined by the enzyme-linked immunosorbent assay. The effects of ASD on A. fumigatus biofilm formation were determined using crystal violet, concanavalin A, safranin staining, and confocal scanning laser microscopy. RESULTS: ASD and A. fumigatus significantly enhanced the production of IL-6 and IL-8 from nasal epithelial cells. By coculturing A. fumigatus with ASD, the dry weight and safranin staining of the fungal biofilms significantly increased in a time-dependent manner. However, the increased level of crystal violet and concanavalin A stain decreased after 72 h of incubation. CONCLUSIONS: ASD and A. fumigatus induced the production of inflammatory chemical mediators from nasal epithelial cells. The exposure of A. fumigatus to ASD enhanced the formation of biofilms. The coexistence of ASD and A. fumigatus may increase the development of fungal biofilms and fungal inflammatory diseases in the sinonasal mucosa.
Asunto(s)
Aspergillus fumigatus , Arena , Aspergillus fumigatus/metabolismo , Biopelículas , Concanavalina A/farmacología , Polvo , Células Epiteliales/metabolismo , Violeta de Genciana/metabolismo , Violeta de Genciana/farmacología , Mediadores de Inflamación/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Mucosa Nasal/metabolismoRESUMEN
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.
Asunto(s)
Polvo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Regulación de la Expresión Génica , Ginsenósidos/farmacología , Mucinas/genética , Panax/química , Arena , Línea Celular , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Ginsenósidos/química , Humanos , Estructura Molecular , Mucina 5AC/biosíntesis , Mucina 5AC/genética , Mucina 5B/biosíntesis , Mucina 5B/genética , Mucinas/biosíntesis , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/metabolismoRESUMEN
Essential oils extracted from plants contain protective volatile compounds and are known to processes antibacterial, antifungal, anti-oxidative, and anti-inflammatory effects. This study was conducted to explore the immunomodulatory effects of essential oil extracted from Chamaecyparis obtusa (EOCO) on house dust mite-induced mucosal inflammation. Cultured primary nasal epithelial cells were stimulated with Dermatophagoides pteronyssinus (DP), and Dermatophagoides farina (DF) for 48 h. The production of interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP) was measured by enzyme-linked immunosorbent assay, and the expression levels of nuclear factor (NF)-κB, activator protein (AP)-1, and mitogen-activated protein kinase (MAPK) were determined by western blot analysis. To examine the effect of EOCO on the production of chemical mediators and the expression of transcription factors, epithelial cells were pretreated with EOCO for 1 h before stimulation. Peripheral blood mononuclear cells (PBMCs) were cultured in nasal epithelial cell conditioned media (NECM) for 72 h, after which the levels of IL-5, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were measured. DP and DF enhanced the production of IL-25, IL-33, and TSLP, and EOCO pretreatment inhibited their production from nasal epithelial cells. EOCO pretreatment also significantly suppressed the expression of NF-κB and AP-1. NECM induced the production of IL-5, IFN- γ, and TNF-α from PBMCs, and only TNF-α production was significantly inhibited by EOCO pretreatment. EOCO pretreatment inhibited the DP and DF induced nasal epithelial cell derived cytokine production and TNF-α production from PBMCs. These results indicate the potential value of EOCO in the treatment of airway inflammatory or immunological diseases.
Asunto(s)
Chamaecyparis/química , Células Epiteliales/efectos de los fármacos , Células Epiteliales/inmunología , Inmunidad/efectos de los fármacos , Factores Inmunológicos , Mucosa Nasal/citología , Aceites Volátiles/farmacología , Pyroglyphidae/inmunología , Adulto , Animales , Células Cultivadas , Citocinas/metabolismo , Depresión Química , Células Epiteliales/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aceites Volátiles/química , Aceites Volátiles/aislamiento & purificación , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
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.
Asunto(s)
Chamaecyparis/química , Factores Inmunológicos/uso terapéutico , Aceites Volátiles/uso terapéutico , Rinitis Alérgica/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Femenino , Inmunoglobulina E/sangre , Factores Inmunológicos/farmacología , Mediadores de Inflamación/metabolismo , Ratones Endogámicos BALB C , Líquido del Lavado Nasal , Mucosa Nasal/efectos de los fármacos , Mucosa Nasal/patología , Aceites Volátiles/farmacología , Ovalbúmina/inmunología , Rinitis Alérgica/sangre , Bazo/patología , Factores de Transcripción/metabolismoRESUMEN
Airborne fungi are associated with upper and lower airway inflammatory diseases. Alternaria is commonly found in nasal secretions and induces the production of chemical mediators from sinonasal mucosa. This study aimed to establish an Alternaria-induced chronic rhinosinusitis (CRS) mouse model and determine the influence of host allergic background on the immunopathological characteristics of CRS. BALB/c mice were used for establishing the CRS model. Alternaria was intranasally instilled for 8 or 16 weeks with or without ovalbumin (OVA) presensitization. Total serum IgE and Alternaria-specific IgE levels were measured by enzyme-linked immunosorbent assay (ELISA). Interleukin (IL)-4, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels in nasal lavage fluid (NLF) and splenocytes were measured by ELISA and their mRNAs and levels of associated transcription factors in sinonasal mucosa were determined with quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). Hematoxylin-eosin staining and periodic acid-Schiff staining were performed to evaluate histological changes. Total serum IgE was increased in both allergic and non-allergic CRS. IL-4 was strongly expressed in NLF in both allergic and non-allergic CRS at 16 weeks and not only eosinophils but also neutrophils were increased in NLF of non-allergic CRS mice. The levels of Th1, Th2, and Treg cytokines and transcription factor mRNAs were significantly increased in sinonasal mucosa of non-allergic CRS mice. Both inflammatory cell infiltration and goblet cell hyperplasia were increased in CRS mice. Repeated intranasal instillation of Alternaria results in sinonasal inflammation with inflammatory cell infiltration. The sinonasal mucosal immune responses against Alternaria were shown to differ depending on the host allergic background.
Asunto(s)
Alternaria/patogenicidad , Rinitis/patología , Sinusitis/patología , Alternaria/inmunología , Animales , Enfermedad Crónica , Modelos Animales de Enfermedad , Femenino , Inmunoglobulina E/sangre , Interleucina-10/análisis , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-4/análisis , Interleucina-4/genética , Interleucina-4/metabolismo , Ratones , Ratones Endogámicos BALB C , Líquido del Lavado Nasal/química , Mucosa Nasal/metabolismo , Mucosa Nasal/patología , ARN Mensajero/metabolismo , Rinitis/inmunología , Sinusitis/inmunología , Bazo/metabolismo , Bazo/microbiología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by mucosal inflammation. Airborne allergens are associated with upper and lower airway inflammatory disease. We investigated the effects of airborne allergen stimulation in the nasal epithelial cells and their effect on the peripheral blood mononuclear cells' (PBMCs) Th immune polarization. Interleukin (IL)-10, IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) levels were determined using the enzyme-linked immunosorbent assay (ELISA) in nasal polyp tissues. Cultured primary nasal epithelial cells were stimulated with Alternaria alternata, Aspergillus fumigatus, Dermatophagoides pteronyssinus (DP), and Dermatophagoides farina (DF) for 48 hours. IL-6, IL-25, IL-33, and TSLP production were measured by ELISA, and the nuclear factor-κB (NF-κB), activator protein 1 (AP-1), and mitogen-activated protein kinase (MAPK) expression were determined by western blot analyses. PBMCs were cultured with nasal epithelial cell-conditioned media (NECM), and IL-5, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were measured. Innate lymphoid type2 cells (ILC2) were analyzed with flowcytometry. IL-25, IL-33, and TSLP levels were significantly higher in eosinophilic nasal polyps. Alternaria, DP, and DF enhanced IL-33 and TSLP production from the nasal epithelial cells through the NF-κB, AP-1, and MAPK pathway. NECM induced IL-5, IFN-γ, and TNF-α production from PBMCs, without increasing ILC2 expression. Alternaria and house dust mites enhanced the chemical mediator production from nasal epithelial cells and these allergens may induce not only Th2 inflammatory responses but also Th1 inflammatory responses in the nasal mucosa.
Asunto(s)
Alternaria/inmunología , Mucosa Nasal/inmunología , Pyroglyphidae/inmunología , Células TH1/inmunología , Células Th2/inmunología , Animales , Citocinas/metabolismo , Susceptibilidad a Enfermedades/inmunología , Humanos , Inmunidad Innata , Mediadores de Inflamación/metabolismo , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Mucosa Nasal/metabolismo , Rinitis/etiología , Rinitis/metabolismo , Rinitis/patología , Sinusitis/etiología , Sinusitis/metabolismo , Sinusitis/patología , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Células TH1/metabolismo , Células Th2/metabolismoAsunto(s)
Productos Biológicos/farmacología , Diferenciación Celular/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Miel , Metaloproteinasa 9 de la Matriz/metabolismo , Pólipos Nasales/patología , Factor de Crecimiento Transformador beta1/farmacología , Acacia , Actinas/genética , Actinas/metabolismo , Supervivencia Celular , Células Cultivadas , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Metaloproteinasa 9 de la Matriz/genética , Fosforilación/efectos de los fármacos , Proteína Smad2/metabolismo , Proteína smad3/metabolismoRESUMEN
BACKGROUND: Upper airway barrier dysfunction has been associated with chronic rhinosinusitis and allergic rhinitis. Alternaria is commonly found in nasal secretion and plays a role in the pathogenesis of airway diseases. The aim of this study was to investigate the effects of Alternaria on the junctional complex of nasal epithelial cells. METHODS: Air-liquid interface nasal epithelial cultures from the inferior turbinate of septal surgery patients were stimulated with Alternaria alternate. Production of intracellular reactive oxygen species (ROS) and transepithelial resistance (TER) was measured. The expression of tight junction (TJ) and adherens junction (AJ) molecules was determined using real-time reverse transcriptase-polymerase chain reaction, Western blot analysis, and confocal microscopy. Protease activity in Alternaria was determined using protease inhibitors and heat inactivation. RESULTS: Alternaria enhanced the production of ROS and reduced the TER. Alternaria decreased the messenger RNA and protein expression of TJs (zonula occludens-1, occludin, and claudin-1), but did not influence the AJ molecule. When Alternaria was pretreated with serine protease inhibitor and heat inactivation, ROS, TER, and TJ molecule expression returned to their nonstimulated levels. CONCLUSION: Serine protease in Alternaria altered nasal epithelial barrier function. Intracellular ROS induced by Alternaria may influence the barrier function of nasal epithelial cells and enhance the inflammatory process of nasal mucosa.
Asunto(s)
Alternaria/enzimología , Células Epiteliales/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Serina Proteasas/metabolismo , Células Cultivadas , Claudina-1/genética , Claudina-1/metabolismo , Humanos , Mucosa Nasal/citología , Ocludina/genética , Ocludina/metabolismo , Proteína de la Zonula Occludens-1/genética , Proteína de la Zonula Occludens-1/metabolismoRESUMEN
The essential oil of Chamaecyparis obtusa (C. obtusa), which is used in soap, toothpaste, and aromatic agents, has been known to have anti-inflammatory properties. In this study, we investigated the effects of microencapsulated C. obtusa essential oil on airborne fungus-induced dendritic cell (DC) activation and Th immune responses. We stimulated monocyte-derived DCs with Alternaria alternate and lipopolysaccharide (LPS). To determine the anti-inflammatory effects, we pre-treated DCs with various concentrations of microencapsulated C. obtusa essential oil and collected the supernatants to measure interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and we determined the expression of cell surface molecules. The effects of the essential oil on CD4+ T cells polarization was determine by culturing stimulated DCs and autologous CD4+ T cells. Alternaria enhanced the production of IL-6 and TNF-α from DCs, and pretreating DCs with 0.001, 0.01, and 0.05% of the essential oil significantly inhibited their production. Increased CD80 and CD86 expression by Alternaria was significantly inhibited with 0.05% of the essential oil. Alternaria-induced IL-5, IL-10, and interferon-gamma from CD4+ T cells were significantly inhibited with C. obtusa essential oil in a dose dependent manner. C. obtusa influenced both Alternaria- and LPS-induced Th1 and Th2 polarization of CD4+ T cells. These results suggest a novel pharmacological use for C. obtusa essential oil to treat inflammatory airway diseases.
Asunto(s)
Chamaecyparis/química , Células Dendríticas/inmunología , Monocitos/inmunología , Aceites Volátiles/farmacología , Células TH1/inmunología , Células Th2/inmunología , Alternaria/química , Cápsulas , Células Dendríticas/citología , Humanos , Interleucina-6/inmunología , Lipopolisacáridos/farmacología , Monocitos/citología , Aceites Volátiles/química , Células TH1/citología , Células Th2/citología , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
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)γ 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 INFγ, 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.
Asunto(s)
Antiinflamatorios/farmacología , Venenos de Abeja/farmacología , Rinitis Alérgica/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Animales , Enfermedad Crónica , Citocinas/biosíntesis , Modelos Animales de Enfermedad , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , FN-kappa B/metabolismo , Mucosa Nasal/metabolismo , Mucosa Nasal/patología , Rinitis Alérgica/inducido químicamente , Rinitis Alérgica/metabolismo , Rinitis Alérgica/patología , Sinusitis/inducido químicamente , Sinusitis/metabolismo , Sinusitis/patología , Factor de Transcripción AP-1/metabolismoRESUMEN
BACKGROUND: The salt-taste threshold can influence the salt appetite, and is thought to be another marker of sodium intake. Many studies have mentioned the relationship between the sodium intake and blood pressure (BP). The aim of this study was to evaluate the relationship between the salt-taste threshold and urinary sodium excretion in normotensive and hypertensive groups. METHODS: We analyzed 199 patients (mean age 52 years, male 47.3%) who underwent 24-h ambulatory BP monitoring (ABPM). Hypertension was diagnosed as an average daytime systolic BP of ≥135 mmHg or diastolic BP of ≥85 mmHg by the ABPM. We assessed the salt-taste threshold using graded saline solutions. The salt-taste threshold, 24-h urinary sodium and potassium excretion, and echocardiographic data were compared between the control and hypertensive groups. RESULTS: The detection and recognition threshold of the salt taste did not significantly differ between the control and hypertensive groups. The 24-h urinary sodium excretion of hypertensive patients was significantly higher than that of the control group (140.9 ± 59.8 vs. 117.9 ± 57.2 mEq/day, respectively, p = 0.011). Also, the urinary sodium-potassium ratio was significantly higher in the hypertensive patients. There was no correlation between the salt-taste threshold and 24-h urinary sodium excretion. CONCLUSIONS: The salt-taste threshold might not be related to the BP status as well as the 24-h urinary sodium excretion.