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Biomedical subjects

Shoji Matsune

Publications and source records attributed to Shoji Matsune.

7 recordsLinked to original sources

TNF-alpha upregulates VCAM-1 and NF-kappaB in fibroblasts from nasal polyps.

OBJECTIVE: Lung and synovial fibroblasts produce VCAM-1 in response to TNF-alpha. However, the massive infiltration of eosinophils, the effects of the increased amount of TNF-alpha and the production of VCAM-1 in human nasal polyp fibroblasts are not yet fully understood. The present study examines the role of VCAM-1 and the molecular mechanism of its expression in nasal fibroblasts. METHODS: Nasal fibroblasts were isolated from human nasal polyps and after four passages, the cells were stimulated with TNF-alpha and VCAM-1 expression was examined by ELISA, flow cytometry, and RT-PCR. The activation of NF-kappaB induced by TNF-alpha was determined by electrophoretic mobility shift assays and the influence on the expression of VCAM-1 was investigated. RESULTS: VCAM-1 protein and mRNA were expressed in unstimulated controls and remarkably increased by TNF-alpha stimulation. NF-kappaB activity was enhanced by TNF-alpha stimulation and remarkably suppressed by NF-kappaB proteasome inhibitor. CONCLUSIONS: The present study discovered that nasal fibroblasts produce VCAM-1 protein and mRNA and that production is increased by TNF-alpha stimulation. Furthermore, VCAM-1 expression in nasal fibroblasts is induced through an NF-kappaB-dependent pathway. These findings might provide a rationale for using NF-kappaB inhibitors as a treatment for nasal inflammatory diseases such as polyps.

Cells, Cultured↗

TNF-alpha and endotoxin increase hypoxia-induced VEGF production by cultured human nasal fibroblasts in synergistic fashion.

OBJECTIVE: Vascular endothelial growth factor (VEGF) promotes angiogenesis and is associated with the invasion and metastasis of malignant tumors. It enhances vascular permeability and is expressed in inflammatory nasal as well as middle-ear mucosa. As the mechanism of VEGF induction during chronic inflammation, such as chronic paranasal sinusitis (CPS) remains to be clarified, we studied the factors regulating the production of VEGF in cultured human nasal fibroblasts and discussed the role of VEGF in the pathogenesis of CPS. METHODS: We used ELISA to quantify VEGF levels in paranasal sinus effusions, nasal secretions, and serum from patients with CPS. In addition, we cultured human nasal fibroblasts isolated from nasal polyps of CPS patients and studied the effects of hypoxia, TNF-alpha, and endotoxin on their production of VEGF using ELISA and PCR. RESULTS: The VEGF concentration was significantly higher in paranasal sinus effusions than in nasal secretions and serum. Nasal fibroblasts produced high levels of VEGF, when cultured under hypoxic condition and this production was remarkably enhanced in the presence of TNF-alpha or endotoxin. CONCLUSION: VEGF is locally produced in paranasal sinuses as well as nasal mucosa and its production is increased in patients with CPS. Hypoxia is associated with the production of VEGF by nasal fibroblasts and TNF-alpha and endotoxin may act synergistically to enhance VEGF production in paranasal sinuses under hypoxic condition.

Analysis of Variance↗

Inhibition of vascular endothelial growth factor by macrolides in cultured fibroblasts from nasal polyps.

OBJECTIVE: In order to study a new mechanism of efficacy of 14-membered ring macrolides in treating chronic rhinosinusitis, inhibitory effects of macrolides on vascular endothelial growth factor production were examined in vitro. METHODS: Vascular endothelisal growth factor production in cultured fibloblasts from human nasal polyps obtained from surgery for chronic paranasal sinusitis stimulated by hypoxia or tumor necrosis factor-alpha was assessed under the administration of Clarithromycin or Roxisthromycin by enzyme linked immunosorbent assay and reverse transcriptase polymerase chain-reaction. RESULTS: Dose-dependent inhibitory effects on vascular endothelisal growth factor production stimulated by hypoxia or tumor necrosis factor-alpha were noted in the groups treated with Clarithromycin and Roxisthromycin, including inhibition of vascular endothelisal growth factor mRNA levels. CONCLUSION: While, to date, several evidences have indicated that the mechanisms by which 14-membered ring macrolides reduce inflammation are not simply bactericidal, these results suggest another new mechanism of efficacy of macrolides in treating chronic rhinosinusitis.

Adult↗

Extravascular papillary endothelial hyperplasia arising from parapharyngeal space.

A 66-year-old man visited our clinic suffering from swelling of right pharyngeal space. He was not aware of other symptoms. The contrast CT showed patchy enhancement with calcification. The enhanced MRI revealed a non-homogeneous signal pattern and patchy central enhancement. During surgery, egg-shaped hard elastic tumor was observed in parapharyngeal space without any sign indicating an invasion into surrounding nerves or feeding vessels. Then the tumor was removed without significant hemorrhage or damage to the cranial nerve. Histological examination of the tumor revealed a nodular lesion with blood clot and hematoma encapsulated with fibrous tissue having vascular spaces of irregular shape and size. From those findings, the tumor was diagnosed as papillary endothelial hyperplasia (PEH). However, since the location of the tumor differed from that of PEH commonly observed in the intravascular space, the tumor was classified as extravascular PEH.

Aged↗

Hypoxia in paranasal sinuses of patients with chronic sinusitis with or without the complication of nasal allergy.

OBJECTIVE: In order to elucidate the pathogenesis of the radiologic opacity of the sinuses frequently observed in patients with allergic rhinitis, the mechanisms underlying their sinus mucosal swelling were studied clinically. MATERIAL AND METHODS: We confirmed the presence of hypoxia in inflamed sinuses and obstruction of the sinus ostium in operated patients with chronic sinusitis by digitally monitoring the oxygen tension. The possibility of radiologic sinus shadow was also investigated after transient obstruction of the natural ostium. RESULTS: The oxygen tension was significantly lower in inflamed than non-inflamed sinuses (p < 0.01), irrespective of the presence or absence of allergic rhinitis. In 54.5% of patients without sinusitis, transient obstruction of the middle meatus by gauze packing resulted in the appearance of a pathologic sinus shadow on radiograms obtained after septoplasty and turbinotomy. In both allergic and non-allergic rhinitis, thick opacity was the most frequently encountered pattern (p < 0.01). CONCLUSION: Our study revealed that in the absence of a primary allergic reaction in the sinus mucosa, blocking of the middle meatus and ostium by allergic swelling of the nasal mucosa may induce hypoxia and secondary mucosal swelling in the sinuses.

Adult↗

The role of nuclear factor-kappa B in interleukin-8 expression by human adenoidal fibroblasts.

OBJECTIVES/HYPOTHESIS: The production of cytokines by adenoids is known to be associated with inflammation of nasopharynx and the pathogenesis of otitis media with effusion. However, the role of adenoids in producing inflammatory cytokines such as interleukin-8 (IL-8) is not yet clear. In the present study, expression of IL-8 in adenoidal fibroblasts was investigated at the level of transcription factors. Further, the effects of clarithromycin, a 14-member ring macrolide, on IL-8 gene expression and nuclear factor-kappa B (NF-kappa B) activation in adenoidal fibroblasts were evaluated. STUDY DESIGN: In vitro study for the production of inflammatory cytokine from human adenoidal fibroblasts. METHODS: Adenoidal fibroblasts were incubated with nontypeable Haemophilus influenzae endotoxin or interleukin-1 beta. Then the expression of IL-8 and the influence of NF-kappa B inhibitor and clarithromycin were evaluated. Interleukin-8 protein production was assessed by ELISA, and IL-8 messenger RNA production was measured by Northern blot analysis and reverse transcriptase-polymerase chain reaction. Activation of NF-kappa B and inhibition of its activation were determined by electrophoretic mobility shift assay. RESULTS: The expression of both IL-8 protein and messenger RNA in adenoidal fibroblasts was enhanced by Haemophilus influenzae endotoxin and interleukin-1 beta and was positively correlated with increases in NF-kappa B activity. Treatment of cells with the NF-kappa B inhibitor N-tosyl-(L)-phenylalanine chloromethyl ketone, as well as with clarithromycin, reduced expression of IL-8 and NF-kappa B activity in a dose-dependent manner. CONCLUSIONS: Results suggest that adenoidal fibroblasts produce IL-8 in response to endotoxin through NF-kappa B activation. The inhibitory effects of clarithromycin on NF-kappa B activation and IL-8 production in adenoidal fibroblasts might explain, in part, the mechanism of this drug in improving otitis media with effusion.

Adenoids↗