PMID- 24925032
OWN - NLM
STAT- MEDLINE
DCOM- 20150629
LR  - 20211021
IS  - 1662-8128 (Electronic)
IS  - 1662-811X (Print)
IS  - 1662-811X (Linking)
VI  - 6
IP  - 6
DP  - 2014
TI  - Porphyromonas gingivalis fimbriae dampen P2X7-dependent interleukin-1beta secretion.
PG  - 831-45
LID - 10.1159/000363338 [doi]
AB  - Porphyromonas gingivalis is a major contributor to the pathogenesis of 
      periodontitis, an infection-driven inflammatory disease that leads to bone 
      destruction. This pathogen stimulates pro-interleukin (IL)-1beta synthesis but not 
      mature IL-1beta secretion, unless the P2X7 receptor is activated by extracellular 
      ATP (eATP). Here, we investigated the role of P. gingivalis fimbriae in 
      eATP-induced IL-1beta release. Bone marrow-derived macrophages (BMDMs) from 
      wild-type (WT) or P2X7-deficient mice were infected with P. gingivalis (381) or 
      isogenic fimbria-deficient (DPG3) strain with or without subsequent eATP 
      stimulation. DPG3 induced higher IL-1beta secretion after eATP stimulation compared 
      to 381 in WT BMDMs, but not in P2X7-deficient cells. This mechanism was dependent 
      on K(+) efflux and Ca(2+)-independent phospholipase A2 activity. Accordingly, 
      non-fimbriated P. gingivalis failed to inhibit apoptosis via the eATP/P2X7 
      pathway. Furthermore, P. gingivalis-driven stimulation of IL-1beta was Toll-like 
      receptor 2 and MyD88 dependent, and not associated with fimbria expression. 
      Fimbria-dependent down-modulation of IL-1beta was selective, as levels of other 
      cytokines remained unaffected by P2X7 deficiency. Confocal microscopy 
      demonstrated the presence of discrete P2X7 expression in the absence of P. 
      gingivalis stimulation, which was enhanced by 381-stimulated cells. Notably, 
      DPG3-infected macrophages revealed a distinct pattern of P2X7 receptor expression 
      with a marked focus formation. Collectively, these data demonstrate that 
      eATP-induced IL-1beta secretion is impaired by P. gingivalis fimbriae in a 
      P2X7-dependent manner.
FAU - Morandini, Ana Carolina
AU  - Morandini AC
AD  - Programa de Imunobiologia, Instituto de Biofisica Carlos Chagas Filho, 
      Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
FAU - Ramos-Junior, Erivan S
AU  - Ramos-Junior ES
FAU - Potempa, Jan
AU  - Potempa J
FAU - Nguyen, Ky-Anh
AU  - Nguyen KA
FAU - Oliveira, Ana Carolina
AU  - Oliveira AC
FAU - Bellio, Maria
AU  - Bellio M
FAU - Ojcius, David M
AU  - Ojcius DM
FAU - Scharfstein, Julio
AU  - Scharfstein J
FAU - Coutinho-Silva, Robson
AU  - Coutinho-Silva R
LA  - eng
GR  - R01 DE009761/DE/NIDCR NIH HHS/United States
GR  - R01 DE019444/DE/NIDCR NIH HHS/United States
GR  - DE 09761/DE/NIDCR NIH HHS/United States
GR  - R01DE019444/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 - 20140606
PL  - Switzerland
TA  - J Innate Immun
JT  - Journal of innate immunity
JID - 101469471
RN  - 0 (IL1B protein, mouse)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Receptors, Purinergic P2X7)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/genetics/immunology
MH  - Animals
MH  - Bacteroidaceae Infections/genetics/*immunology/pathology
MH  - Down-Regulation/genetics/immunology
MH  - Fimbriae, Bacterial/*immunology
MH  - Interleukin-1beta/genetics/*immunology
MH  - Macrophages/*immunology/microbiology/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Myeloid Differentiation Factor 88/genetics/immunology
MH  - Porphyromonas gingivalis/*immunology
MH  - Receptors, Purinergic P2X7/genetics/*immunology
MH  - Toll-Like Receptor 2/genetics/immunology
PMC - PMC4201861
MID - NIHMS593660
EDAT- 2014/06/14 06:00
MHDA- 2015/06/30 06:00
PMCR- 2014/06/06
CRDT- 2014/06/14 06:00
PHST- 2014/02/01 00:00 [received]
PHST- 2014/05/01 00:00 [accepted]
PHST- 2014/06/14 06:00 [entrez]
PHST- 2014/06/14 06:00 [pubmed]
PHST- 2015/06/30 06:00 [medline]
PHST- 2014/06/06 00:00 [pmc-release]
AID - 000363338 [pii]
AID - jin-0006-0831 [pii]
AID - 10.1159/000363338 [doi]
PST - ppublish
SO  - J Innate Immun. 2014;6(6):831-45. doi: 10.1159/000363338. Epub 2014 Jun 6.