Human β-defensin 2 enhances IL-1β production and pyroptosis through P2X7-mediated NLRP3 expression in macrophages  

作　　者：PANPAN WANG GANG LI LI GAO CHUANJIANG ZHAO 

机构地区：[1]Department of Periodontology,Guanghua School and Hospital of Stomatology,Sun Yat-sen University,Guangzhou,China [2]Guangdong Provincial Key Laboratory of Stomatology,Guanghua School and Hospital of Stomatology,Sun Yat-sen University,Guangzhou,China [3]Department of Oral Implantology,Delun Dental,Guangzhou,China

出　　处：《BIOCELL》2022年第5期1197-1207,共11页生物细胞（英文）

基　　金：This work was supported by National Natural Science Foundation of China(NSFC)(81500871);Natural Science Foundation of Guangdong Province(2016A030310214).

摘　　要：Periodontal disease is the leading cause of tooth loss,which is also a high-risk factor for other diseases including oral cancer and cardiovascular disease.Periodontitis is one of the most common type of periodontal diseases.Interleukin-1β(IL-1β)plays a key role in the pathogenesis of periodontitis.However,the mechanism how IL-1βis produced during periodontitis is still unclear.In the present study,we found that humanβ-defensin 2(hBD2)enhances IL-1βproduction through an LPS-primed human acute monocytic leukemia(THP-1)macrophage model.Inhibition of P2X purinoceptor 7(P2X7)reduced hBD2-enhanced IL-1βproduction.Incubation of LPS-primed THP-1 macrophages with potassium chloride also suppressed hBD2-enhanced IL-1βproduction.Silence of inflammasome adaptor Nod-like receptor family pyrin domain containing 3(NLRP3)led to reduced hBD2-enhanced IL-1βproduction.Likewise,inhibition of caspase-1 also resulted in the decrease of IL-1β.Moreover,an ethidium bromide uptake test indicated that hBD2-activated caspase-1 mediated pyroptotic pore formation.Subsequent lactate dehydrogenase detection and flow cytometric analysis indicated that hBD2 also induced pyroptosis.In brief,these findings illustrated not only the mechanism of hBD2 in enhancing the inflammatory response,but also provided novel therapeutic targets for periodontitis.

关 键 词：PERIODONTITIS Humanβ-defensin 2 IL-1Β Signal transduction PYROPTOSIS 

分 类 号：R73[医药卫生—肿瘤]