| Project/Area Number |
15591816
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
TAKENO Sachio Hiroshima University, Hospital, Lecturer, 病院, 講師 (50243556)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2004: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | nasal allergy / sinusitis / eosinophils / cytokines chemokines / helper T cells / CCR4, CXCR3 / transcription factors / steroids / helper T 細胞 / 転写因子NF-kB / グルココルチコイド / CCR4、CXCR3 / NF-κB |
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| Research Abstract |
The division of chronic sinusitis into allergy-associated and non-allergy associated highlights heterogenecity in the celluar profile and the cytokine expression involved in the sinus mucosa. Recent studies have implicated eosinophils as a central player in the persistent inflammation occurring in non-infectious chronic sinusitis. In the present project, we have investigated mechanisms of eosinophil infiltration in sinusitis in relation to allergic rhinitis.
1)We found intimate relation between allergic diathesis and the degree of sinus opacification examined and scored by computed tomography. Patients with high eosinophil infiltration tended to show diffuse sinus diseases not only restricted to the region around the sinus ostia in the lateral nasal wall.
2)We examined cytokine expression and the distribution of CD4-positive cell subsets in the sinus mucosa. The patients with low eosinophilia only showed an increase in IFN-γ mRNA expression. In contrast, the other patients showed similar
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cytokine profiles with high expression levels for GM-CSF, IL-5, eotaxin mRNA. CCR4-positive CD4+ cells were also significantly higher in patients with high eosinophilia, leading to decreased CXCR3+/ CCR4+ cell ratio. These findings provide support for the concept of chronic sinusitis as a Th2-mediated disease process.
3)We examined transcription factor NF-κB activation and concomitant cytokine expression triggered by TNF-α stimulus in cultured sinus epithelial cells. Treatment with TNF-α significantly augmented the degree of NF-κB activation. Further, pretreatment with dexamethazone effectively inhibited the NF-κB activation dose-dependently in the cultured cells. Immunocytochemical analysis also confirmed cellular translocation of p50 subunits with intense nuclear staining as well as concomitant expression of glucocorticoid receptors. These results elucidate the molecular mechanisms responsible for the maintenance of constitutive NF-κB activity in sinus mucosa and would provide a direct causal link between the recruitment of eosinophils and persistence of chronic inflammation. Less
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