title: Are HMGB1 protein expression and secretion markers of upper airways inflammatory diseases?
abstract: Taking into account the mechanisms at the origin of the airways inflammatory pathologies, our attention has been recently addressed to the study of HMGB1, a protein belonging to the group of alarmins. Alarmins are those molecules which in homeostatic conditions carry out specific metabolic and/or structural functions; furthermore, after a direct trauma or an infection, these molecules are released in the extracellular milieu becoming there activators of the innate immunity and powerful inflammatory factors. In a previous research we found in patients affected with chronic rhinosinusitis with/without nasal polyposis (CRSwNP) an increased expression of this protein in the nucleus of nasal mucosa epithelial cells. HMGB1 was overexpressed also as focal subepithelial infiltration and in the inflammatory cells of patients in comparison with controls. These results suggested a possible pathogenetic role of HMGB1 in CRSwNP. The aim of the present study was to investigate if the expression and localization (nuclear, cytoplasmic and extracellular) of the HMGB1 protein-cytokine is somehow related to the severity and complexity of the histological and clinical picture. We noticed values which have around statistical significance between nuclear HMGB1 and eosinophils infiltrate (p=0.0607) and between nuclear HMGB1 and inflammatory infiltrate (P=0.0524). Even more significant was the correlation between extra-cellular HMGB1 expression and the presence of allergic-hyper reactive conditions such as asthma, allergic rhinitis, NSADs intolerance, antibiotic allergy. HMGB1 was significantly more expressed in the nucleus (p=0.0499) and in the intercellular space (p=0.0380) in allergic patients than in non-allergic subjects and as extra-cellular infiltrate in patients with NSADs intolerance (p=0.0022). These results confirm the role of HMGB1 in the pathogenesis of chronic rhinosinusitis with/without nasal polyposis; besides the higher extra-cellular expression in patients with a more severe clinical and inflammatory picture and the presence of associated co-morbidities suggests to seek for new compounds: these compounds, decreasing the extra-cellular release of this alarmin through a scavenger mechanism, could keep under control the inflammatory process without interfering with the nuclear transcriptional messengers.
authors.affiliation: Department of Medical Surgical and Neuro Sciences, O.R.L. Division University of Siena, Siena, Italy.
authors.forename: L M
authors.initials: LM
authors.lastname: Bellussi
authors.forename: C
authors.initials: C
authors.lastname: Iosif
authors.forename: C
authors.initials: C
authors.lastname: Sarafoleanu
authors.forename: E
authors.initials: E
authors.lastname: Jianu
authors.forename: R
authors.initials: R
authors.lastname: Duda
authors.forename: E
authors.initials: E
authors.lastname: Panaitescu
authors.forename: F M
authors.initials: FM
authors.lastname: Passali
authors.forename: D
authors.initials: D
authors.lastname: Passali
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000209:etiology; D015415:Biomarkers; D002908:Chronic Disease; D005260:Female; D024243:HMGB1 Protein / Q000032:analysis / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000209:etiology* / Q000473:pathology; D065631:Rhinitis, Allergic; D012221:Rhinitis, Allergic, Perennial / Q000209:etiology; D012852:Sinusitis / Q000209:etiology* / Q000473:pathology
chemical_list: D015415:Biomarkers; D024243:HMGB1 Protein