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ATP scavenging by the intracellular pathogen Porphyromonas gingivalis inhibits P2X7-mediated host-cell apoptosis.
Title | ATP scavenging by the intracellular pathogen Porphyromonas gingivalis inhibits P2X7-mediated host-cell apoptosis. |
Publication Type | Journal Article |
Year of Publication | 2008 |
Authors | Yilmaz, O, Yao, L, Maeda, K, Rose, TM, Lewis, EL, Duman, M, Lamont, RJ, Ojcius, DM |
Journal | Cell Microbiol |
Volume | 10 |
Issue | 4 |
Pagination | 863-75 |
Date Published | 2008 Apr |
ISSN | 1462-5822 |
Keywords | Adenosine Triphosphate, Apoptosis, Bacterial Proteins, Cells, Cultured, Flow Cytometry, Gingiva, Humans, In Situ Nick-End Labeling, Microscopy, Fluorescence, Nucleoside-Diphosphate Kinase, Porphyromonas gingivalis, Receptors, Purinergic P2, Receptors, Purinergic P2X7 |
Abstract | The purinergic receptor P2X(7) is involved in cell death, inhibition of intracellular infection and secretion of inflammatory cytokines. The role of the P2X(7) receptor in bacterial infection has been primarily established in macrophages. Here we show that primary gingival epithelial cells, an important component of the oral innate immune response, also express functional P2X(7) and are sensitive to ATP-induced apoptosis. Porphyromonas gingivalis, an intracellular bacterium and successful colonizer of oral tissues, can inhibit gingival epithelial cell apoptosis induced by ATP ligation of P2X(7) receptors. A P. gingivalis homologue of nucleoside diphosphate kinase (NDK), an ATP-consuming enzyme, is secreted extracellularly and is required for maximal suppression of apoptosis. An ndk-deficient mutant was unable to prevent ATP-induced host-cell death nor plasma membrane permeabilization in the epithelial cells. Treatment with purified recombinant NDK inhibited ATP-mediated host-cell plasma membrane permeabilization in a dose-dependent manner. Therefore, NDK promotes survival of host cells by hydrolysing extracellular ATP and preventing apoptosis-mediated through P2X(7). |
DOI | 10.1111/j.1462-5822.2007.01089.x |
Alternate Journal | Cell. Microbiol. |
PubMed ID | 18005240 |
PubMed Central ID | PMC2637656 |
Grant List | R01 DE016593-03 / DE / NIDCR NIH HHS / United States R01DE11111 / DE / NIDCR NIH HHS / United States R01DE16593 / DE / NIDCR NIH HHS / United States |