High motility group box 1 (HMGB1) protein and its receptor for advanced glycation end products (RAGE) expression in chronic rhinosinusitis without nasal polyps

Abstract

Introduction. Chronic rhinosinusitis (CRS) affects 14% of the world population. The high motility group box 1 (HMGB1) protein triggers inflammation, cell proliferation and cell survival through its receptor for advanced glycation end products (RAGE) upon release from stressed or necrotic cells. The aim of the study was to analyze the expression and function of HMGB1 and RAGE in CRS, providing more information about HMGB1 signaling pathway in CRS, to determine its potential clinical significance. Material and methods. Thirty-seven patients with CRS and 26 normal controls (NC) were enrolled in this study. Classification of disease severity using the SNOT-20 questionnaire, nasal endoscopy, CT scan, assessment of allergy status, microbiological and cytological analysis was performed in patients. Fresh sinus mucosa samples were obtained and analyzed by immunohistochemistry for HMGB1 and RAGE expression in epithelial cells. ELISA assay was performed to evaluate the concentration of HMGB1 in the patients' sera. Results. No differences were found in HMGB1 immunoexpression between CRS patients and NC, however there was a highly significant difference in RAGE immunoexpression between both groups. There was a correlation between RAGE expression and number of tissue-infiltrating lymphocytes. Further, RAGE expression positively correlated with disease severity and a positive history for allergies. Conclusions. Interaction of HMGB1 and RAGE might be relevant to CRS pathomechanisms leading to sinus mucosa hyperproliferation. CRS pathogenesis might be especially related to the RAGE overexpression correlated with disease severity and allergy.

RAGE and HMGB1 Expression in Orbital Tissue Microenvironment in Graves’ Ophthalmopathy

“…In turn, autoantibodies directed against nucleosomes and double-stranded DNA are characteristics for SLE. Our previous study demonstrated the expression of RAGE and HMGB1 in epithelial cells of sinonasal mucosa samples obtained from patients with chronic rhinosinusitis or in epithelial cells of middle ear cholesteatoma [12,22]. We observed a strong correlation between the disease severity and RAGE expression.…”

“…Paraffin sections of GO patients and NC patients were immunostained using NovoLink Polymer Detection Systems (Novocastra Laboratories, Newcastle, UK) and the following primary antibodies diluted 1 : 100 in Antibody Diluent (Dako): rabbit polyclonal anti-human HMGB1 (LS-C2691, LifeSpan BioSciences, Inc., Seattle, WA, USA) and mouse monoclonal anti-human RAGE (LS-B6042, LifeSpan BioSciences, Inc., Seattle, WA, USA). Deparaffinated and rehydrated sections were stained according to the manufacturer's instructions, as previously described [12]. The activity of endogenous peroxidase was blocked by Peroxidase Block (NovoLink Polymer Detection System; Novocastra Laboratories).…”

HMGB1 in the Pathogenesis of Nasal Inflammatory Diseases and its Inhibition as New Therapeutic Approach: A Review from the Literature

“…In total, 21 articles related to HMGB1 expression in upper airways inflammation and the effects of its blockage by inhibitors in clinical trials have been selected for our review. 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 The search results are summarized in Table 1 .…”

Effects of HMGB1 on Tricellular Tight Junctions via TGF-β Signaling in Human Nasal Epithelial Cells

“…HMGB1 closely contributes to chronic rhinosinusitis with or without nasal polyps [39,40]. Furthermore, HMGB1 disrupts the airway epithelial barrier of human bronchial and lung epithelia via angulin-1/LSR [31,41].…”