Activation of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 6 by Porphyromonas gingivalis regulates programmed cell death in epithelium

Jianru Liu; Wenyi Liu; Peiying Lv; Yixiang Wang; Xiangying Ouyang

Journal of Dental Sciences (Oct 2023)

Activation of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 6 by Porphyromonas gingivalis regulates programmed cell death in epithelium

Jianru Liu,
Wenyi Liu,
Peiying Lv,
Yixiang Wang,
Xiangying Ouyang

Affiliations

Jianru Liu: Department of Periodontology, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, China
Wenyi Liu: Department of Periodontology, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, China
Peiying Lv: Department of Periodontology, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, China
Yixiang Wang: Central Laboratory, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, China; Biobank, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, China; Corresponding author. Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China.
Xiangying Ouyang: Department of Periodontology, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, China; Corresponding author. Department of Periodontology, Peking University School and Hospital of Stomatology, No. 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China.

Journal volume & issue: Vol. 18, no. 4
pp. 1867 – 1875

Abstract

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Background/purpose: Gingival epithelial cells form a physiological barrier against bacterial invasion. Programmed cell death (PCD) regulated by pathogen precognition receptors (PRRs) lead to tissue destruction and is closely related to inflammatory diseases. The purpose of this study was to investigate whether nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 6 (NLRP6) expresses in periodontal epithelium and induces PCD of epithelial cells infected by Porphyromonas gingivalis (P. gingivalis), therefore involves in periodontitis. Material and methods: The expression of NLRP6 was detected in periodontal epithelium from human gingival sections and HaCaT cells stimulated by P. gingivalis. NLRP6 was over-expressed by adenovirus infection in HaCaT or knocked down by siRNA in P. gingivalis infected HaCaT, and the cell death was observed by transmission electron microscopy and flow cytometry analysis. In addition, qPCR and Western blot were performed to determine the expression of NLRP6 and the pyroptosis excutors, caspase-1 and gasdermin D. Enzyme-linked immunosorbent assay were performed to detect the secretion of IL-1β and IL-18. Results: NLRP6 was up-regulated in both gingival epithelium of patients with periodontitis and P. gingivalis infected HaCaT. Over-expression of NLRP6 in HaCaT led to caspase-1 dependent pyroptosis. Interestingly, knockdown of NLRP6 with siRNA followed by P. gingivalis stimulation inhibited pyroptosis and induced apoptosis. Conclusion: Up-regulation of NLRP6 by P. gingivalis in HaCaT led to pyroptosis, while knocking down NLRP6 inhibited pyroptosis and induced apoptosis, which indicated this PRR may play a crucial role in periodontitis by regulating PCD in periodontal epithelium.

Published in Journal of Dental Sciences

ISSN: 1991-7902 (Print)
Publisher: Elsevier
Country of publisher: Taiwan, Province of China
LCC subjects: Medicine: Dentistry
Website: http://www.journals.elsevier.com/journal-of-dental-sciences/

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