title: Porphyromonas gingivalis modulates Pseudomonas aeruginosa-induced apoptosis of respiratory epithelial cells through the STAT3 signaling pathway.
abstract: Pseudomonas aeruginosa is an important opportunistic bacterial pathogen, causing infections of respiratory and other organ systems in immunocompromised hosts that may invade and proliferate in mucosal epithelial cells to induce apoptosis. Previous studies suggest that oral bacteria, especially gram-negative periodontal pathogens, may enhance P. aeruginosa invasion into respiratory epithelial cells to augment tissue destruction. In this study, we investigated the effect of the periodontopathogen Porphyromonas gingivalis on P. aeruginosa-induced epithelial cell apoptosis. P. gingivalis invasion transiently inhibited P. aeruginosa-induced apoptosis in respiratory epithelial cells via the signal transducer and activator of transcription 3 (STAT3) signaling pathway. The activated STAT3 up-regulated the downstream anti-apoptotic moleculars survivin and B-cell leukemia-2 (bcl-2). This process was accompanied by down-regulation of pro-apoptosis molecular Bcl-2-associated death promoter (bad) and caspase-3 activity inhibition. In addition, the activation of the STAT3 pathway was affected by P. gingivalis in a dose-dependent manner. Finally, co-invasion of P. aeruginosa and P. gingivalis led to greater cell death compared with P. aeruginosa challenge alone. These results suggest that regulation of P. aeruginosa-induced apoptosis by P. gingivalis contributes to the pathogenesis of respiratory disease. Interference with this process may provide a potential therapeutic strategy for the treatment and prevention of respiratory disease.
authors.affiliation: Department of Oral Biology and Periodontics, School of Stomatology, China Medical University, Nanjing North St. 117, Shenyang 110002, Liaoning Province, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Oral Biology and Periodontics, School of Stomatology, China Medical University, Nanjing North St. 117, Shenyang 110002, Liaoning Province, China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Pan
authors.affiliation: Department of Oral Biology and Periodontics, School of Stomatology, China Medical University, Nanjing North St. 117, Shenyang 110002, Liaoning Province, China.
authors.forename: Di
authors.initials: D
authors.lastname: Teng
authors.affiliation: Department of Oral Biology and Periodontics, School of Stomatology, China Medical University, Nanjing North St. 117, Shenyang 110002, Liaoning Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Oral Biology and Periodontics, School of Stomatology, China Medical University, Nanjing North St. 117, Shenyang 110002, Liaoning Province, China.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Kou
authors.affiliation: Department of Oral Biology, School of Dental Medicine, 109 Foster Hall, University at Buffalo, State University of New York, 3435 Main St., Buffalo, NY 14214-3092, USA.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Haase
authors.affiliation: Department of Oral Biology, School of Dental Medicine, 109 Foster Hall, University at Buffalo, State University of New York, 3435 Main St., Buffalo, NY 14214-3092, USA.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Scannapieco
authors.affiliation: Department of Oral Biology and Periodontics, School of Stomatology, China Medical University, Nanjing North St. 117, Shenyang 110002, Liaoning Province, China; Department of Oral Biology, School of Dental Medicine, 109 Foster Hall, University at Buffalo, State University of New York, 3435 Main St., Buffalo, NY 14214-3092, USA. Electronic address: yppan@mail.cmu.edu.cn.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Pan
mesh_terms: D017209:Apoptosis / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D016966:Porphyromonas gingivalis / Q000378:metabolism* / Q000472:pathogenicity; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000378:metabolism* / Q000472:pathogenicity; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000382:microbiology*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D000077022:Survivin; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; D000077022:Survivin; D051025:bcl-Associated Death Protein; D053148:Caspase 3
keywords: Apoptosis; Porphyromonas gingivalis; Pseudomonas aeruginosa; Respiratory infection; Signal transduction pathway