Resveratrol protects against asthma-induced airway inflammation and remodeling by inhibiting the HMGB1/TLR4/NF-κB pathway.

Abstract

The aim of the present study was to explore the protective role of resveratrol (RES) in asthma-induced airway inflammation and remodeling, as well as its underlying mechanism. An asthma rat model was induced by ovalbumin (OVA) treatment. Rats were randomly assigned into sham, asthma, 10 µmol/l RES and 50 µmol/l RES groups. The amount of inflammatory cells in rat bronchoalveolar lavage fluid (BALF) was detected. Pathological lesions in lung tissues were accessed by hematoxylin and eosin (H&E), and Masson's trichrome staining. Levels of inflammatory factors in lung homogenate were detected via ELISA. The blood serum of asthmatic and healthy children was also collected for analysis. Reverse transcription-quantitative polymerase chain reaction was performed to detect high mobility group box 1 (HMGB1), Τoll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MyD88) and NF-κB expression in asthmatic and healthy children, as well as rats of the different groups. H&E staining demonstrated that multiple inflammatory cell infiltration into the rat airway epithelium of the asthma group occurred whilst the 50 µmol/l RES group displayed alleviated pathological lesions. Masson staining indicated that there was an increased airway collagen deposition area in the asthma and 10 µmol/l RES groups compared with the 50 µmol/l RES group. The number of inflammatory cells in BALF extracted from rats of the asthma and 10 µmol/l RES groups was higher compared with the 50 µmol/l RES group. Treatment with 50 µmol/l RES significantly decreased the thicknesses of the airway wall and smooth muscle. ELISA results illustrated that interleukin (IL)-1, IL-10 and tumor necrosis factor-α (TNF-α) levels were elevated, whereas IL-12 level was reduced in lung tissues of the asthma and 10 µmol/l RES groups whilst the 50 µmol/l RES group demonstrated the opposite trend. HMGB1, TLR4, MyD88 and NF-κB mRNA levels were remarkably elevated in rats of the asthma and 10 µmol/l RES groups compared with the 50 µmol/l RES group. Serum levels of IL-1, IL-10 and TNF-α were elevated, whereas IL-12 was reduced in asthmatic children compared with healthy children. The present results demonstrated that a large dose of RES alleviated asthma-induced airway inflammation and airway remodeling by inhibiting the release of inflammatory cytokines via the HMGB1/TLR4/NF-κB pathway.