上睑下垂
炎症体
自噬
牙周炎
巨噬细胞
炎症
半胱氨酸蛋白酶1
PI3K/AKT/mTOR通路
肺泡巨噬细胞
医学
药理学
细胞生物学
癌症研究
化学
免疫学
生物
信号转导
内科学
细胞凋亡
生物化学
体外
作者
Zhenxing Zhao,Ming Ye,Xiang Li,Hao Tan,Xinyi He,Lan Yang,Jinlin Song,Leilei Zheng
摘要
Macrophage pyroptosis drives the secretion of IL-1β, which has been recently reported to be a featured salivary biomarker for discriminating periodontitis in the presence of diabetes. This study aimed to explore whether macrophage pyroptosis plays a role in the development of diabetes mellitus-periodontitis, as well as potential therapeutic strategies. By establishing a model of experimental diabetes mellitus-periodontitis in rats, we found that IL-1β and gasdermin D were highly expressed, leading to aggravated destruction of periodontal tissue. MCC950, a potent and selective molecule inhibitor of the NLRP3 inflammasome, effectively inhibited macrophage pyroptosis and attenuated alveolar bone losses in diabetes mellitus-periodontitis. Consistently, in vitro, high glucose could induce macrophage pyroptosis and thus promoted IL-1β production in macrophages stimulated by lipopolysaccharide. In addition, autophagy blockade by high glucose via the mTOR-ULK1 pathway led to severe oxidative stress response in macrophages stimulated by lipopolysaccharide. Activation of autophagy by rapamycin, clearance of mitochondrial ROS by mitoTEMPO, and inhibition of inflammasome by MCC950 could significantly reduce macrophage pyroptosis and IL-1β secretion. Our study demonstrates that hyperglycemia promotes IL-1β production and pyroptosis in macrophages suffered by periodontal microbial stimuli. Modulation of autophagy activity and specific targeting of the ROS-inflammasome pathway may offer promising therapeutic strategies to alleviate diabetes mellitus-periodontitis.
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