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

Xiang Liang,Yang Shen,Xiaowei Zhang,Guangxiang He,Guolin Tan

doi:10.1038/s41598-021-85785-3

Xiang Liang, Yang Shen + Show 3 more

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https://doi.org/10.1038/s41598-021-85785-3

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Abstract

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.

Highlights

High mobility group box 1 (HMGB1) has been known to involve in the pathogenesis of many inflammatory diseases
The colony formation unit (CFU) value was only a slight decrease in group 4 and 5, compared with group 2 and 3 (p > 0.05). These findings suggested that Merocel packing could induce an acute rhinosinusitis (ARS) model that verified by following pathological examination
The main strains of bacteria in secretion of ARS rats were identified by Maldi-Tof mass spectrometry, and it included Proteus mirabilis, Klebsiella pneumoniae, and Morganella morganii in group 2 to 5

Summary

Introduction

High mobility group box 1 (HMGB1) has been known to involve in the pathogenesis of many inflammatory diseases. 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). 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. There are evidences that an increased expression of HMGB1 was associated with the pathogenesis of chronic rhinosinusitis with/without nasal polyps, and secreted HMGB1 correlated with severity of inflammation in chronic rhinosinusitis[5] The role it playing in ARS remains unclear. Recent studies demonstrated that EP attenuated inflammatory response of murine allergic rhinitis by decreasing HMGB1 expression[7] It remains to be elucidated whether EP plays anti-inflammatory effects in ARS by inhibiting HMGB1 signals

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