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ABSTRACT: Rationale: Epithelial cells at mucosal surfaces are integral components of innate and adaptive immunity. IL-25 is reportedly produced by epithelial cells and likely plays vital roles in regulating type-2 immune responses. However, little has been known regarding the mechanisms that control production and extracellular releases of IL-25. Objective: We hypothesized that proteases from the multiple allergens may induce IL-25 production in airway epithelial cell. Method and Results: In this study, we found that IL-25 is constitutively produced and detectable in cytoplasm of resting normal human bronchial epithelial (NHBE) cells. When exposed to airborne allergens, such as house dust mite (HDM), stored IL-25 was released rapidly to the extracellular space. IL-25 release was not accompanied by cell death, suggesting involvement of active secretory mechanism(s). HDM also enhanced IL-25 mRNA transcription, which was dependent on their protease activities. Furthermore, activation of NHBE cells with authentic proteases, such trypsin and papain, or with a peptide agonist for protease-activated receptor-2 was sufficient to enhance IL-25 mRNA transcription and protein. Protease-driven increase in mRNA transcription and allergen-driven extracellular release of IL-25 protein was also observed in primary nasal epithelial cells (PNECs) from healthy individuals. Conclusion: These findings suggest that IL-25 production by airway epithelial cells is regulated by the transcription and protein release levels, and that allergen proteases likely play pivotal roles in both biological processes.
American Journal of Respiratory Cell and Molecular Biology 04/2013; · 5.13 Impact Factor
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ABSTRACT: Mucormycosis is a rapidly progressive fungal infection that usually occurs in patients with diabetes mellitus or in immunocompromised patients. Sinus involvement is the most common clinical presentation and the rates of mortality increase with the orbital extension. The treatment of mucormycosis includes aggressive surgical debridement and systemic antifungal therapy. Early diagnosis and prompt initiation of effective antifungal drugs are essential for successful outcome. However, the role of orbital exenteration for the case of orbital involvement remains controversial, and the drugs effective against mucormycosis are limited. We present a successfully treated case with rhino-orbital mucormycosis caused by Rhizopus oryzae in a diabetic and dialysis patient. The early diagnosis, surgical debridement and a new combination therapy with liposomal amphotericin B and micafungin were effective. This new combination antifungal therapy will be useful for the treatment of mucormycosis.
Auris, nasus, larynx 05/2011; 39(2):224-8. · 0.58 Impact Factor
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ABSTRACT: Heparin is one of the most important anticoagulant drugs. It has been known that heparin also possesses anti-inflammatory activities. Mucus hypersecretion is an important characteristic of airway inflammation. However, little is known about the regulatory effects of heparin on mucus hypersecretion in airway epithelial cells. To elucidate the anti-inflammatory function of heparin in airway epithelial cells, we examined the in vivo effects of heparin on mucus hypersecretion and neutrophil infiltration in rat nasal epithelium. We also examined the in vitro effects of heparin on mucin production and IL-8 secretion from cultured human airway epithelial cells.
We induced hypertrophic and metaplastic changes of goblet cells in rat nasal epithelium by intranasal lipopolysaccharide (LPS) instillation. The effects of intranasal instillation with heparin on mucus production and neutrophil infiltration were examined. in vitro effects of heparin on airway epithelial cells were examined using cultured NCI-H292 cells. Mucus secretion was evaluated by enzyme-linked immunosorbent assay using an anti-MUC5AC monoclonal antibody.
Intranasal instillation with unfractionated heparin (UFH; 100 IU/0.1 mL) or low molecular weight heparin (LMWH; 100 IU/0.1 mL) at 30 minutes before LPS instillation significantly inhibited LPS-induced mucus production and neutrophil infiltration in rat nasal epithelium. UFH or LMWH inhibited tumor necrosis factor alpha (10 ng/mL)-induced secretion of MUC5AC and IL-8 from NCI-H292 cells in a dose-dependent manner (0.01-10 IU/mL). MUC5AC mRNA expression was also significantly inhibited.
These results indicate that heparin inhibits airway mucus hypersecretion in airway epithelial cells directly and indirectly through the suppression of IL-8 secretion and neutrophil infiltration.
American Journal of Rhinology and Allergy 03/2011; 25(2):69-74.
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ABSTRACT: Thrombin, the effector enzyme of the coagulation system, has been reported to promote inflammatory responses in nasal diseases through its protease-activated receptors (PARs). Chronic rhinosinusitis (CRS) is characterized by increased deposition of extracellular matrix proteins, tissue remodeling, and formation of nasal polyps. The role of thrombin in chronic nasal inflammation-associated tissue remodeling still has not been appraised. This study was conducted to elucidate the role of thrombin in the pathogenesis of CRS.
Nasal secretion was collected from patients with CRS with nasal polyp (CRSwNP) with asthma (n = 9), CRSwNP without asthma (n = 10), allergic rhinitis (n = 7), and control patients (n = 3). The concentrations of thrombin, thrombin-antithrombin (TAT) complex, and vascular endothelial growth factor (VEGF) were evaluated by enzyme immunoassays. The concentration of thrombin and TAT complex was measured in nasal secretion from each group of patients, and VEGF was measured in culture medium from airway epithelial cells treated with thrombin or thrombin receptor agonist peptide.
Thrombin and TAT complex were significantly increased in nasal secretion of patients with CRSwNPs with asthma compared with the control group. Thrombin and PAR-1 agonist peptide significantly stimulated VEGF secretion from cultured human airway epithelial cells.
The results of this study showed that there is increased activation of the coagulation system in the nasal mucosa of CRS patients and that thrombin may play a role in nasal polyp formation by stimulating VEGF production from airway epithelial cells.
American Journal of Rhinology and Allergy 01/2011; 25(1):7-11.
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ABSTRACT: We report the endoscopic ligation of the maxillary and sphenopalatine arteries for the treatment of intractable epistaxis. From March 2003 to February 2005, 17 patients (12 men, 5 women) with epistaxis were hospitalized in our department. Patient age ranged from 25 to 83 years, with an average age of 62 years. 8 patients were successfully treated using the conventional packing method, 2 patients were treated using electrocauterization, and 1 patient with macroglobulinemia was treated using plasma exchange therapy. 6 patients underwent endoscopic ligation of the maxillary and sphenopalatine arteries while under general anesthesia. The post operative courses were uneventful, and no recurrent bleeding has been noted. Endscopic ligation of the maxillary and sphenopalatine arteries is safer than intraarterial embolization and less invasive than conventional surgical approach for the ligation of maxillary artery. This technique appears to be a safe and effective surgical treatment for patients with intractable epistaxis.
Nippon Jibiinkoka Gakkai Kaiho 09/2006; 109(8):649-54.
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ABSTRACT: Endoscopic resection of nasal and paranasal sinus tumors is more aesthetic and less invasive than conventional resection, such as Luc's operation and lateral rhinotomy. We clarified the effect of radical endoscopic tumor excision and the control of local bleeding hazardous in endoscopic surgery. Subjects were patients with benign lesions in the nasal cavity, medial wall of the maxillary sinus, ethmoid sinus, and/or sphenoid sinus without concurrent malignant lesions. Although patients selection for malignant tumor excision was based on (1) possible en bloc resection, (2) low-grade malignant tumors, and (3) tumors in the nasal cavity and adjoining paranasal sinus, the final decision was made individual. Subjects were 23 patients with benign tumor (10 inverted papilloma, 9 hemangioma, 2 juvenile angiofibroma, and 2 other tumors) and 4 with malignant tumor (olfactory neuroblastoma, acinic cell carcinoma, squamous cell carcinoma, and chondroid chordoma) in the nasal and paranasal sinus. The tumor was resected en bloc except for patients with inverted papilloma (2 cases) and chondroid chordoma. Recurrence in benign tumors was zero during a mean observation of 21 months. One with chondroid chordoma, however, suffered a recurrent lesion 7 months after the initial operation. The lesion was successfully salvaged by a similar endoscopic procedure and subsequently treated with electron beam irradiation. Preoperative arterial embolization, laser coagulation, and ligation of the sphenopalatine artery were very useful in reducing blood loss during surgery and maintaining a clear endoscopic view. In intraoperative bleeding volume, less than 100 ml of bleeding occurred during surgery in 23 of 27 patients. The endoscopic excision of benign lesions in the nasal and paranasal sinus is thus as effective as conventional radical surgery. Endoscopic removal of malignant lesions remains controversial because of the small number of patients and short postoperative observation.
Nippon Jibiinkoka Gakkai Kaiho 08/2005; 108(7):724-33.
