Resveratrol Attenuates Ankylosing Spondylitis in Mice by Inhibiting the TLR4/NF-κB/NLRP3 Pathway and Regulating Gut Microbiota

炎症体 TLR4型 封堵器 肿瘤坏死因子α 促炎细胞因子 势垒函数 白藜芦醇 肠道菌群 双歧杆菌 免疫学 白细胞介素 炎症 失调 乳酸菌 微生物学 医学 药理学 生物 细胞因子 紧密连接 生物化学 细胞生物学 发酵
作者
Ming-Hui Ding,Peng-Gang Xu,Ying Wang,Bao-di Ren,Junli Zhang
出处
期刊:Immunological Investigations [Taylor & Francis]
卷期号:52 (2): 194-209 被引量:9
标识
DOI:10.1080/08820139.2022.2154162
摘要

Ankylosing spondylitis (AS) is an autoimmune disease associated with disturbed gut microbiota. Currently, the treatments and outcomes of AS are not satisfactory. It is reported that resveratrol (RES) is a major phytoalexin with anti-inflammatory, antibacterial and some other pharmacological effects. However, there are no studies on the role of RES in AS. Therefore, this study aimed to explore the effect and mechanism of RES on AS. Proteoglycan and complete freund's adjuvant were used to conduct an AS mouse model, and then the AS mice were gavaged with RES (20 mg/kg and 50 mg/kg) daily for 4 weeks. Subsequently, the effect of RES on AS mice was assessed by detecting disease severity, inflammatory cytokines, NLRP3 inflammasome, TLR4/NF-κB pathway, intestinal mucosal barrier function, intestinal microbial barrier function. The assessment results indicated that RES could significantly relieve progression and severity of AS, inhibit the expression of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6, interleukin-17A, interferon-γ), and promote the expression of anti-inflammatory cytokines (interleukin-4). RES intervention caused the inhibition of NLRP3 inflammasome and TLR4/NF-κB pathway. In terms of intestinal barrier function, experimental results found RES increased zonula occludens-1 and occludin expression, and additionally, changed the composition of the gut microbiota by increasing levels of Lactobacillus and Bifidobacterium and reducing levels of Enterococcus faecalis and Escherichia coli. Collectively, RES protects PG-induced AS mice by inhibiting inflammatory responses and TLR4/NF-κB/NLRP3 pathway, restoring intestinal mucosal barrier function, and regulating the composition of the gut microbiota. In other words, RES is a potential candidate for the treatment of AS.
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