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

Cappello

et al. 2017

Multidiscip Respir Med

BackgroundMucociliary clearance is the main self-clearing system of the nasal cavity and paranasal sinuses.This is a very important means of non specific defence against continuous organic and inorganic contamination conveyed by air. It works by trapping particles and microorganisms in the mucus and then by transporting the mucous film to the pharynx where it is eliminated with a cough or swallowed. Its congenital or acquired abnormalities are involved in the occurrence of widespread infectious and often severe nose and paranasal sinuses diseases; generally concerning the rhinopharyngealtubal district.Restoring mucociliary clearance of the nasal epithelium when altered thus represents a key therapeutic tool against rhinosinus chronic diseases.This study evaluates the clinical efficacy of the inhalation of a natural compound (Narivent® nasal spray) in chronic vasomotor rhinitis.MethodsThe study involved 79 patients suffering from chronic vasomotor rhinitis presenting an increased mucociliary clearance time. Patients were randomized into 2 groups: a first group of 49 subjects and a second group of 30 subjects.The first group was treated with a nasal spray (Narivent® nasal spray) (2 sprays per nostril twice a day) for 30 days.The second group was treated with a nasal spray containing isotonic solution in the same way and for the same period of the first group.Nasal Mucociliary transport time was measured in the patients of both groups before treatment, after 15 days of treatment, and at the end of the 30 days treatment.ResultsThe study shows how one of the treatments carried out determines a major objective reduction of the mucociliary clearance time in the patients under examination, using the method which involves the use of an insoluble coloured tracer (vegetable carbon), bringing the values back within normal range. At the end of the study we objectivated an increase in the rate of mucociliary transport in 97.9% percentage of patients we enrolled.ConclusionsThis study shows the effectiveness of treatment with natural extracts with nasal mucosa restoring function in the treatment of chronic vasomotor rhinitis, a nasal inflammatory disease characterized by morphological and functional alteration of the normal nasal mucosa.

Section: Discussionmentioning

confidence: 99%

Nasal Muco-ciliary transport time alteration: efficacy of 18 B Glycyrrhetinic acid

Cappello

et al. 2017

Multidiscip Respir Med

“…HMGB1 binds to Toll-like receptor 4 (TLR-4) and the receptor for advanced glycation end products (RAGE), activating the NF-κB signaling pathway and inducing the release of pro-inflammatory mediators, cytokines and chemokines 15 . It has been shown to play a role in the pathogenesis of several inflammatory diseases like hepatitis, arthritis, stroke, liver and kidney ischemia, sepsis, rheumatoid arthritis, systemic lupus erithematosus 16 . Recently, studies demonstrated that HMGB1 was highly expressed in epithelial cells and inflammatory cells of patients with chronic rhinosinusitis and allergic rhinitis, and patients with severe symptoms have the highest serum levels and the highest extracellular expression of HMGB1 5 , 17 .…”

Section: Discussionmentioning

confidence: 99%

Ethyl pyruvate ameliorate inflammatory response of sinonasal mucosa by inhibiting HMGB1 in rats with acute rhinosinusitis

Xiang

Shen

Zhang

et al. 2021

Sci Rep

High mobility group box 1 (HMGB1) has been known to involve in the pathogenesis of many inflammatory diseases. The aim of this study was to establish animal model of acute rhinosinusitis (ARS), and determine whether ethyl pyruvate (EP) attenuate inflammatory response of sinonasal mucosa by inhibiting HMGB1 in ARS animals. Thirty-six Sprague Dawley (SD) rat were used as follows: six normal controls without intervention (group 1); thirty rats were used for establishment of ARS rats model by nasal insertion of Merocel sponge, and model rats without any treatments (group 2), treated with nasal drops of sterile saline (group 3), 10 μl EP (group 4), and 20 μl EP (group 5), twice a day for 5 days, respectively. Bacterial culture was done regularly and the main bacterial strains were identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry. HMGB1 expression in sinonasal mucosa was detected by immunohistochemistry and RT-PCR. Serum levels of HMGB1, IL-6, and TNF-α were determined by ELISA. Data from 29 of 36 rats that had completed research were analyzed. Bacterial colony formation unit (CFU) of nasal secretion was significantly higher in each group of ARS rats compared with controls (p < 0.001). ARS rats treated with EP had only slightly decreased CFU, but significantly attenuated inflammatory response of sinonasal mucosa and decreased HMGB1 expression compared to those treated with saline alone (p < 0.001). Serum levels of HMGB1, IL-6 and TNF-α were significantly higher in ARS rats compared to controls, and decreased by EP treatments (p < 0.001). Nasal sponge packing led to acute inflammatory response of nasal sinus in rats, and increased the expression of HMGB1, IL-6, and TNF-α. Nasal drops with EP could attenuate the inflammation of sinonasal mucosa through inhibiting the expression of HMGB1, IL-6 and TNF-α in ARS rats.

“…Additionally, NAL fluid is more safely and easily collected from patients (i.e., via nasal irrigation) relative to procedures involving tissue harvesting or blood sampling. A review described previous studies evaluating the importance of HMGB1 in upper airway inflammatory diseases, such as rhinosinusitis and allergic rhinitis; however, the analyses were performed using nasal tissue 51 . In this analysis, we found only a limited number of studies using NAL fluid 5 , 8 , 19 , 22 .…”

Section: Discussionmentioning

confidence: 99%

Concentrations of HMGB1 and Hsp70 of healthy subjects in upper and lower airway: Literature Review and Meta-analysis

Min¹,

Kim²,

Choi³

et al. 2021

Int. J. Med. Sci.

Although high-mobility group box 1 and heat-shock protein 70 are implicated in airway diseases and suggested as relevant diagnostic biomarkers, their control concentrations in the airways have not yet been determined. This study aimed to evaluate concentration of healthy subjects for both these proteins in the upper and lower airways via meta-analysis. We searched MEDLINE, EMBASE, and Google Scholar for articles describing concentration of healthy subjects for these proteins. Data from healthy populations were combined using a random-effects model, and subgroup and sensitivity analyses were performed to determine between-study heterogeneity. We analyzed 22 studies involving 485 patients. Concentration of healthy subjects of high-mobility group box 1 and heat-shock protein 70 varied from “not detected” to 326.13 ng/mL and from 0.20 pg/mL to 9240.00 pg/mL, respectively, with the values showing significant heterogeneity. Subgroup analysis for high-mobility group box 1 revealed 13.63 ng/mL (95% CI 12.13-15.14), 100.31 ng/mL (95% CI -31.28-231.91), 9.54 ng/mL (95% CI 8.91-10.17), and 65.82 ng/mL (95% CI 55.51-76.14) for the lower airway, upper airway, pediatric populations, and adults, respectively, whereas that for heat-shock protein 70 revealed 20.58 pg/mL (95% CI 7.87-33.29) for the lower airway and 9240.00 ±11820 pg/mL for the upper airway. Although concentrations of healthy subjects of these proteins varied in the upper and lower airways, the levels of both these proteins were higher in the upper airway than in the lower airway, and these concentrations differed according to the age and sampling procedure. Our findings support the further evaluation of these proteins as biomarkers for airway-related diseases.