GroEL triggers NLRP3 inflammasome activation through the TLR/NF-κB p-p65 axis in human periodontal ligament stem cells  

作　　者：Li Zhang Mengmeng Duan Xiaohua Pu Huiling Zheng Xinjie Ning Ying Tu Chunming Xu Demao Zhang Chengcheng Liu Jing Xie 

机构地区：[1]State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu 610041,China [2]School of Basic Medicine,Gannan Medical University,Ganzhou 341000,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第9期1340-1351,共12页生物化学与生物物理学报（英文版）

摘　　要：The interaction between bacteria and the host plays a vital role in the initiation and progression of systemic diseases,including gastrointestinal and oral diseases,due to the secretion of various virulence factors from these pathogens.GroEL,a potent virulence factor secreted by multiple oral pathogenic bacteria,is implicated in the damage of gingival epithelium,periodontal ligament,alveolar bone and other peripheral tissues.However,the underlying biomechanism is still largely unknown.In the present study,we verify that GroEL can trigger the activation of NLRP3 inflammasome and its downstream effector molecules,IL-1βand IL-18,in human periodontal ligament stem cells(hPDLSCs)and resultantly induce high activation of gelatinases(MMP-2 and MMP-9)to promote the degradation of extracellular matrix(ECM).GroEL-mediated activation of the NLRP3 inflammasome requires the participation of Toll-like receptors(TLR2 and TLR4).High upregulation of TLR2 and TLR4 induces the enhancement of NF-κB(p-p65)signaling and promotes its nuclear accumulation,thus activating the NLRP3 inflammasome.These results are verified in a rat model with direct injection of GroEL.Collectively,this study provides insight into the role of virulence factors in bacteria-induced host immune response and may also provide a new clue for the prevention of periodontitis.

关 键 词：GROEL NLRP3 inflammasome TLR NF-kB signaling PERIODONTITIS 

分 类 号：R781.42[医药卫生—口腔医学]