Adenovirus-Mediated ICOSIg Gene Therapy in a Presensitized Murine Model of Allergic Rhinitis.

Allergic rhinitis is a chronic inflammatory disease of the upper airways caused by Th2 cell-type cytokines in response to allergen exposure. The inducible costimulator (ICOS), the third member of the CD28/CTLA4 family, plays an important role in immune response. In this study, adenovirus vectors containing ICOSIg (Adex1CAICOSIg) were administered to effectively inhibit the ICOS/ICOSL interaction, and the effects of Adex1CAICOSIg on allergic rhinitis were examined. Intranasal administration of Adex1CAICOSIg attenuated airway inflammation, as demonstrated by a decrease in nasal symptoms and infiltration of eosinophils into the nasal mucosa, as well as by a decrease in local IL-5 expression. Therefore, the ICOS/ICOSL pathway significantly contributes to the progression of allergic rhinitis.

Vascular tumors of the external auditory canal: three case reports and a review of the literature.

BACKGROUND: Benign vascular tumors are frequently found in the head and neck, however, such tumors of the external auditory canal are extremely rare. We report three cases of benign vascular tumors limited to the external auditory canal. CASE DESCRIPTION: A 50-year-old woman was diagnosed during an episode of ear fullness and hearing loss. A 10-year-old boy consulted our department about an episode of recurrent otorrhagia. A 20-year-old man found a bulge of his external auditory canal by chance. Complete surgical resection was performed for the first patient. The second patient underwent electro-coagulation of the lesion. In the third patient, to exclude the possibility of a malignant tumor, a biopsy was performed under local anesthesia. Histopathological analysis demonstrated the characteristic of vascular tumors. The lesion showed remarkable reduction during his treatment with antibiotics and cleaning. He remains under careful observation. DISCUSSION AND EVALUATION: In diagnosis, there is sometimes confusion between vascular tumors and malformations. Generally, vascular malformations can be differentiated from vascular tumors since they are present at birth and are generally stable. CONCLUSION: Decision making about treatment of benign vascular tumors is sometimes confusing because of the difficulty in diagnosis. We performed biopsy for only one of our three cases because we regard that informal biopsy should not be conducted for lesions with difficult hemostic conditions and locations.

Distribution of specific binding sites for cysteinyl leukotriene 1 receptor antagonist in human nasal mucosa.

CONCLUSION: The high density of [3H]-pranlukast binding sites on the local leukocytes in human nasal mucosa suggests that CysLT1 receptor antagonists may directly modulate cellular function of the local leukocytes through binding to CysLT1 receptor on allergic nasal mucosa. OBJECTIVES: The cysteinyl leukotrienes (CysLTs) are lipid mediators that have been implicated in the pathogenesis of allergic diseases. Pharmacological studies using CysLTs indicate that two classes of receptors named CysLT1 and CysLT2 receptor exist. The former is sensitive to the CysLT1 receptor antagonist currently used to treat asthma and allergic rhinitis. To confirm the binding sites of CysLT1 receptor antagonist in human nasal mucosa, the autoradiographic distribution of CysLT1 receptor was studied in human nasal inferior turbinates. MATERIALS AND METHODS: Cryostat sections were incubated with [3H]-pranlukast for autoradiography. Nonspecific binding was determined by adding unlabelled pranlukast. RESULTS: Autoradiograms indicated [3H]-pranlukast densely labeled on the interstitial cells. Blood vessels were sparsely labeled. There was no specific labeling in the submucosal glands or epithelium. These results support our previous report from in situ hybridization and immunohistochemistry of CysLT1 receptor.

Expression and localization of steroid receptors in human nasal mucosa.

OBJECTIVE: To investigate the expression of glucocorticoid receptor (GR), oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) in nasal mucosa. MATERIAL AND METHODS: Human turbinates were obtained after turbinectomy from seven patients. The expression and localization of steroid receptors were examined using reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: Using RT-PCR, GR and ER alpha mRNA were detected in all cases. In contrast, ER beta, PR and AR mRNA were found in five, four and six cases, respectively. Using immunohistochemistry, antibodies to GR showed the presence of GR within all cells of nasal mucosa, with the highest quantities of GR being localized in epithelial cells, submucosal glands and inflammatory leukocytes. Immunohistochemical analysis of sex steroid receptor revealed that anti-ER alpha antibody labelled mainly mast cells and anti-ER beta antibody labelled submucosal glands, and that no PR or AR expression was detected in any of the samples tested. CONCLUSIONS: The role of ER in mast cells and submucosal glands has not been well clarified. However, precise knowledge of the identity and distribution of sex steroid receptor should be of considerable interest in understanding the role of sex hormones in upper airway diseases such as allergic and non-allergic rhinitis.

Tributyltin (TBT) increases TNFα mRNA expression and induces apoptosis in the murine macrophage cell line in vitro.

OBJECTIVE: Tributyltin (TBT) compounds have been widely used as antifouling agents for shipbottom paint. The immune system is a target of TBT intoxication. We evaluated the effects of TBT chloride in macrophages, which have critical roles in the immune system, using a murine macrophage lineage cell line, J774.1,in vitro. METHODS: We examined tumor necrosis factor α (TNFα), interleukin-1ß (IL-1ß) andc-jun mRNA expression in J774.1 cells. The effects of TBT on the apoptosis of J774.1 cells were examined by determining the percentage of TUNEL-positive cells and caspase-3 activity. RESULTS: The mean values of the viabilities of J774.1 cells exposed to TBT decreased dose-dependently. The relative mRNA expression of TNFα increased dose-dependently, however, that of IL-1ß was not significantly different among the groups. The mean percentage of TUNEL-positive cells increased dose-dependently. Increases in the caspase-3 activities of J774.1 cells were observed in the groups exposed to higher concentrations of TBT. The mean value of relative mRNA expression of c-Jun transcription factor increased dose-dependently. CONCLUSIONS: The increases in the percentage of TUNEL-positive cells and in caspase-3 activity suggested that exposure to TBT induces apoptosis of J774.1 cells. The increases in the mRNA expression of TNFα andc-jun by TBT may be related to apoptosis in macrophages.

Tumor necrosis factor increases MUC1 mRNA in cultured human nasal epithelial cells.

OBJECTIVE: Mucins are high molecular weight glycoproteins which are normally expressed on the surface of a variety of epithelia. It is possible that shedding of such molecules from the epithelium could play a role in preventing bacterial colonization at the mucosal surface. Immunohistochemical and reverse transcriptase polymerase chain reaction(RT-PCR) analyses of human inferior turbinates have shown the existence of MUC1 mucin in nasal mucosa. However, the regulatory mechanisms of MUC1 mucin are poorly understood. In order to clarify the modulation of mucin gene expression, we developed a real-time semi-quantitative RT-PCR based on TaqMan fluorescence methodology to quantify MUC1 mRNA in primary cultured human nasal epithelial cells (HNECs). MATERIAL AND METHODS: HNECs were stimulated with recombinant human tumor necrosis factor (TNF)-alpha (20 pg/ml to 20 ng/ml) for specified time periods (0, 12, 24 and 48 h) and MUC1 mRNA was determined by means of semi-quantitative RT-PCR. RESULTS: Significant increases in MUC1 gene expression in HNECs were initially detected at 12 h, peaking at 24 h after stimulation. TNF-mediated MUCI mRNA expression at 24 h was significantly inhibited by co-incubation with human recombinant soluble TNF receptor. CONCLUSIONS: TNF-mediated MUC1 gene expression may contribute to the pathogenesis of human inflammatory upper airway disorders. Also, our mucin mRNA real-time PCR provides a quantitative method for investigating the regulation of mucin gene expression in both healthy and diseased samples.