The role of High Mobility Group Box 1 chromosomal protein in the pathogenesis of chronic sinusitis and nasal polyposis.
Chronic rhinosinusitis with nasal polyposis is considered to be a multifactorial disease where different stimuli (mechanical, viral, bacterial, fungal infection, immunological disorders or dysreactivity, environmental pollution), acting on the mucosa of nasal cavities and paranasal sinuses, lead to epithelial damage and mucosal inflammation. Inflammatory cell infiltration (predominantly eosinophils, but also neutrophils, mast cells, macrophages and lymphocytes), cytokine release and sub-epithelial oedema are the histological pictures that are associated, from the clinical point of view, with nasal congestion, secretion and/or post-nasal drip and facial pain/headache. Recently, the importance of the HMG B-1 protein in the pathogenesis of several inflammatory diseases has been demonstrated. This protein is released from necrotic/damaged cells or immune-activated cells, and by acting on specific membrane receptors causes the release of pro-inflammatory mediators, endothelial activation and the survival of inflammatory cells. The objective of the present study was: i) to determine whether HMG B1 is augmented in chronic rhinosinusitis with nasal polyps; ii) if its expression is associated with eosinophils, TNF-α, IL 5 and IL 8 cytokines typically present in chronic inflammation of the nose and paranasal sinuses; iii) to investigate a hypothetical role of this protein in the pathogenesis of nasal polyposis. Nasal polyps tissue from 21 patients affected by CRSwNP and nasal mucosa from 8 controls was collected at the ENT Department of the Chinese PLA General Hospital and underwent immunohistological staining for detection of HMG B1 protein and IL -5, IL -8 and TNF-α inflammatory cytokines. The degree of HMG B1 protein expression was evaluated by dividing the stained sections in 4 portions: 1) nucleus of epithelial cells, 2) cytoplasm of epithelial cells, 3) focal extracellular infiltration, 4) inflammatory cells. HMG B1 was more expressed in the nucleus of epithelial cells of patients compared with controls. In contrast, epithelial cytoplasm HMG B1 staining was significant lower in patients. Sub-epithelial focal infiltration of HMG B1 protein expression was lower in controls, whereas the expression of HMG B1 in the inflammatory cells in patients was significantly increased in comparison with controls. These data, together with the correlation we found between HMG B1 protein expression in different portions and the number of eosinophils infiltrating cells, or IL -5, IL -8 and TNF-α positive cells in patients, suggest that HMG B1 may play a crucial role in the pathogenesis of chronic rhinosinusitis with nasal polyps.
Department of Human Pathology and Oncology, O.R.L. Division, University of Siena, viale Bracci, Siena, Italy. l.bellussi@virgilio.it
L M
LM
Bellussi
L
L
Chen
D
D
Chen
F M
FM
Passali
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D
Passali
D000328:Adult; D002908:Chronic Disease; D005260:Female; D024243:HMGB1 Protein / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000150:complications / Q000209:etiology*; D012220:Rhinitis / Q000150:complications / Q000209:etiology; D012852:Sinusitis / Q000150:complications / Q000209:etiology*; D055815:Young Adult
D024243:HMGB1 Protein
Chronic rhinosinusitis; HMGB1 chromosomal protein; Nasal polyposis