ORIGINAL ARTICLE The Effect of Porphyromonas gingivalis Lipopolysaccharide on the Pyroptosis of Gingival Fibroblasts Yu-Yang Li, 1,2 Qing Cai, 1 Bao-Sheng Li, 1 Shu-Wei Qiao, 1,2 Jia-Yang Jiang, 1,2 Dan Wang, 1,2 Xue-Chun Du, 1,2 and Wei-Yan Meng 1,3 Received 26 August 2020; accepted 27 October 2020 Abstract— Periodontitis is a chronic inflammatory disease induced by Porphyromonas gingi- valis (P. gingivalis) and other pathogens. P. gingivalis release various virulence factors inc- luding lipopolysaccharide (LPS). However, whether P. gingivalis–LPS inducing pyroptosis in human gingival fibroblasts (HGFs) remains unknown. In present study, P. gingivalis–LPS decreased the membrane integrity of HGFs, and pyroptosis-associated cytokines were upre- gulated at the mRNA level. In addition, pyroptosis proteins were highly expressed in gingival tissues of periodontitis. P. gingivalis–LPS induced gingivitis in the rat model, and the expression level of pyroptosis-associated proteins increased. Together, P. gingivalis–LPS can activate the pyroptosis reaction, which may be a pro-pyroptosis status in a relative low concentration. KEY WORDS: Porphyromonas gingivalis; lipopolysaccharide; fibroblast; programmed cell death; pyroptosis. INTRODUCTION Periodontitis is a chronic progressive disease devel- oped from gingival inflammation to alveolar resorption, which is mainly caused by multiple pathogens [1], while several associated risk factors, such as smoking, defective prosthesis, and systemic diseases, may aggravate its pro- gression [2]. Periodontitis has a high incidence worldwide [3], while the mechanism of periodontium destruction at the molecular level remains unclear. P. gingivalis is one of the main pathogens involved in periodontal diseases, and plays an important role in the development of the disease [4]. The bacteria and their metabolites activate multi- proteins oligomers, which may motivate immunoreaction and induce damage to the host cells [5]. Programmed cell death (PCD) is a regulated cell death mediated by a range of gene expression levels, including apoptosis, necroptosis, and pyroptosis [6]. Apo- ptosis is the active process that contributes to the elimina- tion of injured cells and regeneration of healthy cells [7], and is regulated by caspase-3 and caspase-7 activation [8]. At present, apoptotic cells present in the periodontium are strongly correlated with periodontitis, confirming the role of apoptosis in periodontitis [9]. However, apoptosis may lead to pathogen elimination even before triggering host 1 Department of Dental Implantology, Hospital of Stomatology, Jilin University, Changchun, Jilin, China 2 Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Changchun, Jilin, China 3 To whom correspondence should be addressed at Department of Dental Implantology, Hospital of Stomatology, Jilin University, Changchun, Jilin, China. E-mail: mengsitong66@163.com 0360-3997/20/0000-0001/0 # 2020 Springer Science+Business Media, LLC, part of Springer Nature Inflammation ( # 2020) DOI: 10.1007/s10753-020-01379-7