PMID- 25828169 OWN - NLM STAT- MEDLINE DCOM- 20151215 LR - 20240213 IS - 1769-714X (Electronic) IS - 1286-4579 (Print) IS - 1286-4579 (Linking) VI - 17 IP - 5 DP - 2015 May TI - Porphyromonas gingivalis attenuates ATP-mediated inflammasome activation and HMGB1 release through expression of a nucleoside-diphosphate kinase. PG - 369-77 LID - S1286-4579(15)00062-3 [pii] LID - 10.1016/j.micinf.2015.03.010 [doi] AB - Many intracellular pathogens evade the innate immune response in order to survive and proliferate within infected cells. We show that Porphyromonas gingivalis, an intracellular opportunistic pathogen, uses a nucleoside-diphosphate kinase (NDK) homolog to inhibit innate immune responses due to stimulation by extracellular ATP, which acts as a danger signal that binds to P2X7 receptors and induces activation of an inflammasome and caspase-1. Thus, infection of gingival epithelial cells (GECs) with wild-type P. gingivalis results in inhibition of ATP-induced caspase-1 activation. However, ndk-deficient P. gingivalis is less effective than wild-type P. gingivalis in reducing ATP-mediated caspase-1 activation and secretion of the pro-inflammatory cytokine, IL-1beta, from infected GECs. Furthermore, P. gingivalis NDK modulates release of high-mobility group protein B1 (HMGB1), a pro-inflammatory danger signal, which remains associated with chromatin in healthy cells. Unexpectedly, infection with either wild-type or ndk-deficient P. gingivalis causes release of HMGB1 from the nucleus to the cytosol. But HMGB1 is released to the extracellular space when uninfected GECs are further stimulated with ATP, and there is more HMGB1 released from the cells when ATP-treated cells are infected with ndk-deficient mutant than wild-type P. gingivalis. Our results reveal that NDK plays a significant role in inhibiting P2X7-dependent inflammasome activation and HMGB1 release from infected GECs. CI - Copyright (c) 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. FAU - Johnson, Larry AU - Johnson L AD - Department of Molecular Cell Biology, University of California, Merced, CA 95343, USA; Health Sciences Research Institute, University of California, Merced, CA 95343, USA. FAU - Atanasova, Kalina R AU - Atanasova KR AD - Department of Periodontology, University of Florida, Gainesville, FL 32610, USA; Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610, USA. FAU - Bui, Phuong Q AU - Bui PQ AD - Department of Molecular Cell Biology, University of California, Merced, CA 95343, USA; Health Sciences Research Institute, University of California, Merced, CA 95343, USA. FAU - Lee, Jungnam AU - Lee J AD - Department of Periodontology, University of Florida, Gainesville, FL 32610, USA; Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610, USA. FAU - Hung, Shu-Chen AU - Hung SC AD - Department of Molecular Cell Biology, University of California, Merced, CA 95343, USA; Health Sciences Research Institute, University of California, Merced, CA 95343, USA. FAU - Yilmaz, Ozlem AU - Yilmaz O AD - Department of Periodontology, University of Florida, Gainesville, FL 32610, USA; Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610, USA. Electronic address: oyilmaz@ufl.edu. FAU - Ojcius, David M AU - Ojcius DM AD - Department of Molecular Cell Biology, University of California, Merced, CA 95343, USA; Health Sciences Research Institute, University of California, Merced, CA 95343, USA. Electronic address: david.ojcius@gmail.com. LA - eng GR - R01 DE019444/DE/NIDCR NIH HHS/United States GR - R01DE019444/DE/NIDCR NIH HHS/United States GR - R01 DE016593/DE/NIDCR NIH HHS/United States GR - R01DE016593/DE/NIDCR NIH HHS/United States GR - R56 DE016593/DE/NIDCR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150327 PL - France TA - Microbes Infect JT - Microbes and infection JID - 100883508 RN - 0 (HMGB1 Protein) RN - 0 (Inflammasomes) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - EC 2.7.4.6 (Nucleoside-Diphosphate Kinase) SB - IM MH - Adenosine Triphosphate/metabolism MH - Cells, Cultured/microbiology MH - Gingiva/cytology MH - HMGB1 Protein/immunology/*metabolism MH - Humans MH - Inflammasomes/*immunology/metabolism MH - Nucleoside-Diphosphate Kinase/immunology/*metabolism MH - Porphyromonas gingivalis/*immunology/pathogenicity MH - Signal Transduction/drug effects PMC - PMC4426005 MID - NIHMS673985 OTO - NOTNLM OT - Inflammation OT - Innate immunity OT - Interleukins OT - Porphyromonas gingivalis OT - Purinergic receptor COIS- Conflict of interest: The authors declare no conflict of interest. EDAT- 2015/04/02 06:00 MHDA- 2015/12/17 06:00 PMCR- 2016/05/01 CRDT- 2015/04/02 06:00 PHST- 2015/03/19 00:00 [received] PHST- 2015/03/19 00:00 [accepted] PHST- 2015/04/02 06:00 [entrez] PHST- 2015/04/02 06:00 [pubmed] PHST- 2015/12/17 06:00 [medline] PHST- 2016/05/01 00:00 [pmc-release] AID - S1286-4579(15)00062-3 [pii] AID - 10.1016/j.micinf.2015.03.010 [doi] PST - ppublish SO - Microbes Infect. 2015 May;17(5):369-77. doi: 10.1016/j.micinf.2015.03.010. Epub 2015 Mar 27.