Affiliation:
1. The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei‐MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology Wuhan University Wuhan China
2. Department of Periodontology, School & Hospital of Stomatology Wuhan University Wuhan China
Abstract
AbstractPorphyromonas gingivalis is involved in the pathogenesis of multiple polymicrobial biofilm–induced inflammatory diseases, including apical periodontitis, and it triggers pyroptosis accompanied by robust inflammatory responses. Tet methylcytosine dioxygenase 1 (TET1), an epigenetic modifier enzyme, has been is correlated with inflammation, though an association of TET1 and P. gingivalis–related pyroptosis in cementoblasts and the molecular mechanisms has not been shown. Our study here demonstrated that P. gingivalis downregulated Tet1 expression and elicited CASP11‐ and GSDMD‐dependent pyroptosis. Additionally, Tet1 mRNA silencing in cementoblasts appeared to result in a more severe pyroptotic phenotype, where levels of CASP11 and GSDMD cleavage, lactate dehydrogenase release, and IL‐1β and IL‐18 production were significantly increased. Moreover, Tet1 overexpression resulted in blockade of pyroptosis activation accompanied by inflammation moderation. Further analyses revealed that TET1 modulated glycolysis, confirmed by the application of the specific inhibitor 2‐deoxy‐d‐glucose (2‐DG). The pyroptosis phenotype enhanced by Tet1 silencing was moderated by 2‐DG upon P. gingivalis invasion. Taken together, these data show the effects and underlying mechanisms of TET1 on pyroptosis and inflammatory phenotype induced by P. gingivalis in cementoblasts, and provides insight into the involvement of P. gingivalis in apical periodontitis and, possibly, other inflammatory diseases.
Funder
National Natural Science Foundation of China
Fundamental Research Funds for the Central Universities
Subject
History and Philosophy of Science,General Biochemistry, Genetics and Molecular Biology,General Neuroscience
Cited by
6 articles.
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