title: Porphyromonas gingivalis induces autophagy in THP-1-derived macrophages.
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.
authors.affiliation: Department of Oral Microbiology, School of Dentistry, Pusan National University, Yangsan, South Korea.
authors.forename: M H
authors.initials: MH
authors.lastname: Park
authors.affiliation: Department of Oral Microbiology, School of Dentistry, Pusan National University, Yangsan, South Korea.
authors.forename: S Y
authors.initials: SY
authors.lastname: Jeong
authors.affiliation: Department of Oral Microbiology, School of Dentistry, Pusan National University, Yangsan, South Korea.
authors.forename: H S
authors.initials: HS
authors.lastname: Na
authors.affiliation: Department of Oral Microbiology, School of Dentistry, Pusan National University, Yangsan, South Korea.
authors.forename: J
authors.initials: J
authors.lastname: Chung
mesh_terms: D000818:Animals; D000071182:Autophagosomes; D001343:Autophagy / Q000276:immunology / Q000502:physiology*; D002454:Cell Differentiation; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008247:Lysosomes; D008264:Macrophages / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D010518:Periodontitis / Q000378:metabolism / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000472:pathogenicity*
chemical_list: D016207:Cytokines
keywords: 
  Porphyromonas gingivalis
  ; autophagy; autophagy-related 5; beclin-1; light chain 3