2007 Fiscal Year Final Research Report Summary
Molecular analysis of effects of gtucocorticoids on eosinophilic rhinosinusitis with reference to regulation of inflammatory transcription factors.
| Project/Area Number |
18591868
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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, Graduate School of Biomedical Sciences, Associate Professor (50243556)
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| Project Period (FY) |
2006 – 2007
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| Keywords | eosinophils / sinusitis / steroids / glucocorticoid receptor (GR) / transcription factors / toll-like receptor (TLR) / nuclear factor-kappa B / cytokines |
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| Research Abstract |
Recent studies have implicated eosinophils as a central player in the persistent inflammation occurring in non-infectious chronic sinusitis. The mechanisms by which eosinophilic inflammation damages the epithelium and contributes to recurrent acute exacerbations in the disease have not been fully elucidated. In the present project, we have investigated molecular mechanisms of effectiveness of nasal steroids in relation to intracellular regulation by transcription factors.
1) We examined cytokine expression and the distribution of glucocorticoid receptor (GR) -positive cells in the sinus muffin The patients with high eosinophilia showed higher density of GR type β distribution in the sinus mucosa. The tendency was dominant especially in infiltrating inflammatory cells in the ethmoid sinus mucosa. The use of nasal steroids effectively attenuated Th2 cytokine expression.
2)We examined transcription factor NF-kB activation and concomitant cytokine expression triggered by LPS and PGN stimulus
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in cultured sinus epithelial cells. The results clearly demonstrate an increase of NF-kB p50 activity after the stimulation in a dose-dependent manner. Pretreatment with glucocorticoids (GCs) effectively inhibited the p50 activation. Immunocytochemical analysis confirmed cellular translocation of p50 subunits into the nucleus with concomitant expression of glucocorticoid receptors and toll-like receptors (TLRs) 2 and 4 in culture cells. These results elucidate the potent anti-inflammatory effects of GCs and inflammatory signal pathways induced though TLRs in paranasal sinus epithelial cells.
3)We assessed whether topical instillation of beclomethasone dipropionate dry powder onto the paranasal sinus improved the clinical and radiological conditions after appropriate surgical intervention. Improvement in the endoscopic appearance scores was obtained in 91.4% of patients and the result was better than that from the previous study (71.7%). Significant decreases in the avenged CT scores were also noted from 5.62 to 1.93 after treatment. We consider that this novel technique is effective for the post-surgical treatment of the disease through the control of the inflammatory process that persists in the sinus cavity. Less
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