| Chronic rhinosinusitis with nasal polyps (CRSwNP) is defined as chronic inflammationof the nose and paranasal sinuses. Factors contributing to CRSwNP include infection(viral, bacterial, fungal), allergy and muco-ciliary clearance impairment. Histologically,damage to the nasal epithelium accompanied by the infiltration of inflammatory cellsand subepithelial oedema can be found. As inflammation, in the broadest sense, shouldbe considered as a protective physiological response to infection and injuries, these in-flammatory cells, in turn, release a range of mediators and cytokines (IL-5, IL-8, TNF-α,IFN-γ and RANTES, et al.), leading to the amplication of the inflammatory process.Recently, the important role of the HMGB1protein in the pathogenesis of several acuteor chronic inflammatory diseases has been demonstrated. HMGB1causes therecruitment of inflammatory cells (eosinophils and neutrophils, et al.) and stimulation ofproinflammatory mediators. Thereby HMGB1protein can be regarded as a bridgelinking innate and adaptive immune responses. HMGB1was found to be upregulated inthe epithelium with COPD and the nasal secretions with allergic rhinitis. However, themechanism has not been reported. The aim of our present study was to evaluateexpression and mechanism of HMGB1by immunohistochemical, Western blot andRT-PCR analysis in the CRSwNP. This study provides a theoretical basis and reliablelead compound for the further development of the CRSwNP.Part one:Expression of High Mobility Group Box Chromosomal Protein1in chronicrhinosinusitis with nasal polypsObjectives: To investigate whether high mobility group box1(HMGB1) is augmentedin the Chinese eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) and ifnon-eosinophilic CRSwNP is associated with IL-5, IL-8, and TNF-α.Methods: Nasal polyps specimens collected from41patients with CRSwNP (20eosinophilic and21non-eosinophilic). Biopsies of uncinate process, ethmoidal mucosal,or inferior turbinate from9non-CRS patients were used as controls by means ofimmunohistochemistry, quantitative RT-PCR and Western blot.Results: By immunohistochemistry, there was a significantly increased expression level of HMGB1-positive epithelium together with an extensive eosinophil infiltration inCRSwNP as compared with controls. The band of HMGB1in eosinophilic CRSwNPwas stronger than those in non-eosinophilic CRSwNP and controls (P=0.044and0.001,respectively). The mRNA levels of HMGB1, IL-5, IL-8, and TNF-α were significantlyhigher in eosinophilic CRSwNP than those from controls and non-eosinophilicCRSwNP, but no significant differences of these markers between the non-eosinophilicCRSwNP and controls. HMGB1expression levels correlated significantly andpositively with IL-5, IL-8, and TNF-α (rs=0.665,0.771, and0.724; P<0.001respectively) and slightly with eosinophil infiltration (rs=0.149; P=0.012) and the bloodeosinophils count (rs=0.225; P=0.001) in all samples.Conclusion: Upregulation of HMGB1could be a significant marker typically ineosinophilic CRSwNP and it may also contribute to the pathogenesis of CRSwNP alongwith IL-5, IL-8, and TNF-α.Part two:Expression of High Mobility Group Box Chromosomal Protein1in LPS-inducedcultured human nasal epithelial cellsObjectives: To investigate the expression of HMGB1in LPS-induced human nasalepithelial cells in vitro.Methods: The expression and translocation of HMGB1in the cytoplasm, nuclei andculture medium of the exposed epithelial cells were determined using Western blottingand immunofluorescence assay.Results: Compared with the control cells, the cells exposed to100μg/ml LPS for24hshowed significantly increased levels of HMGB1in the epithelial cells (P<0.05) andexposure for48h significantly increased HMGB1expression in the cuture medium(P<0.01). HMGB1translocation from the nuclei to the cytoplasm occurred after24h.Conclusion: LPS can induce HMGB1translocation and release in human nasalepithelial cells in vitro, suggesting the involvement of HMGB1in chronic rhinosinusitiswith nasal polyps. |
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