No abstract

Autophagy provides a mechanism for the turnover of cellular organelles and proteins through a lysosome-dependent degradation pathway and is a possible mechanism in inflammatory disease. Periodontitis is an inflammatory disease caused by periodontal pathogens. Porphyromonas gingivalis, an important periodontal pathogen, activates cellular autophagy to provide a replicative niche while suppressing apoptosis in endothelial cells. However, the molecular basis for a causal relationship between P. gingivalis and autophagy is unclear. This research examines the involvement of P. gingivalis in autophagy through light chain 3 (LC3) and autophagic proteins, and the role of P. gingivalis-induced autophagy in the clearance of P. gingivalis and inflammation. To investigate the molecular mechanism of autophagy induced by P. gingivalis, PMA-differentiated THP-1-derived macrophages were infected with live P. gingivalis. The P. gingivalis increased the formation of autophagosomes in a multiplicity of infection-dependent manner, as well as autophagolysosomes. Porphyromonas gingivalis activated LC3-I/LC3-II conversion and increased the conjugation of autophagy-related 5 (ATG5) -ATG12 and the expression of Beclin1. The expressions of Beclin1, ATG5-ATG12 conjugate, and LC3-II were significantly inhibited by the presence of 3-methyladenine, an autophagy inhibitor. Interestingly, 3-methyladenine increased the survival of P. gingivalis and proinflammatory cytokine interleukin-1β production. The data indicate that P. gingivalis induces autophagy in PMA-differentiated THP-1-derived macrophages and in turn, macrophages eliminate P. gingivalis through an autophagic response, which can lead to the restriction of an excessive inflammatory response by downregulating interleukin-1β production. The induction of autophagy by P. gingivalis may play an important role in the periodontal inflammatory process and serve as a target for the development of new therapies.