PMID- 24566622
OWN - NLM
STAT- MEDLINE
DCOM- 20140605
LR  - 20211021
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Print)
IS  - 0019-9567 (Linking)
VI  - 82
IP  - 5
DP  - 2014 May
TI  - Diverse Toll-like receptors mediate cytokine production by Fusobacterium 
      nucleatum and Aggregatibacter actinomycetemcomitans in macrophages.
PG  - 1914-20
LID - 10.1128/IAI.01226-13 [doi]
AB  - Toll-like receptors (TLRs) orchestrate a repertoire of immune responses in 
      macrophages against various pathogens. Fusobacterium nucleatum and 
      Aggregatibacter actinomycetemcomitans are two important periodontal pathogens. In 
      the present study, we investigated TLR signaling regulating cytokine production 
      of macrophages in response to F. nucleatum and A. actinomycetemcomitans. TLR2 and 
      TLR4 are redundant in the production of cytokines (interleukin-6 [IL-6] and tumor 
      necrosis factor alpha [TNF-alpha]) in F. nucleatum- and A. 
      actinomycetemcomitans-infected macrophages. The production of cytokines by 
      macrophages in response to F. nucleatum and A. actinomycetemcomitans infection 
      was impaired in MyD88-deficient macrophages. Moreover, cytokine concentrations 
      were lower in MyD88-deficient macrophages than in TLR2/TLR4 (TLR2/4) 
      double-deficient cells. An endosomal TLR inhibitor, chloroquine, reduced cytokine 
      production in TLR2/4-deficient macrophages in response to F. nucleatum and A. 
      actinomycetemcomitans, and DNA from F. nucleatum or A. actinomycetemcomitans 
      induced IL-6 production in bone marrow-derived macrophages (BMDMs), which was 
      abolished by chloroquine. Western blot analysis revealed that TLR2/4 and MyD88 
      were required for optimal activation of NF-kappaB and mitogen-activated protein 
      kinases (MAPKs) in macrophages in response to F. nucleatum and A. 
      actinomycetemcomitans, with different kinetics. An inhibitor assay showed that 
      NF-kappaB and all MAPKs (p38, extracellular signal-regulated kinase [ERK], and Jun 
      N-terminal protein kinase [JNK]) mediate F. nucleatum-induced production of 
      cytokines in macrophages, whereas NF-kappaB and p38, but not ERK and JNK, are 
      involved in A. actinomycetemcomitans-mediated cytokine production. These findings 
      suggest that multiple TLRs may participate in the cytokine production of 
      macrophages against periodontal bacteria.
FAU - Park, Se-Ra
AU  - Park SR
AD  - Department of Pathology and Research Center for Oral Disease Regulation of the 
      Aged, School of Dentistry, Chosun University, Gwangju, South Korea.
FAU - Kim, Dong-Jae
AU  - Kim DJ
FAU - Han, Seung-Hyun
AU  - Han SH
FAU - Kang, Min-Jung
AU  - Kang MJ
FAU - Lee, Jun-Young
AU  - Lee JY
FAU - Jeong, Yu-Jin
AU  - Jeong YJ
FAU - Lee, Sang-Jin
AU  - Lee SJ
FAU - Kim, Tae-Hyoun
AU  - Kim TH
FAU - Ahn, Sang-Gun
AU  - Ahn SG
FAU - Yoon, Jung-Hoon
AU  - Yoon JH
FAU - Park, Jong-Hwan
AU  - Park JH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140224
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Cytokines)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Aggregatibacter actinomycetemcomitans/*physiology
MH  - Animals
MH  - Cytokines/genetics/*metabolism
MH  - Fusobacterium Infections/immunology/metabolism/microbiology
MH  - Fusobacterium nucleatum/*physiology
MH  - Gene Expression Regulation/physiology
MH  - Macrophages/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Pasteurellaceae Infections/immunology/metabolism/microbiology
MH  - Toll-Like Receptors/genetics/*metabolism
PMC - PMC3993440
EDAT- 2014/02/26 06:00
MHDA- 2014/06/06 06:00
PMCR- 2014/11/01
CRDT- 2014/02/26 06:00
PHST- 2014/02/26 06:00 [entrez]
PHST- 2014/02/26 06:00 [pubmed]
PHST- 2014/06/06 06:00 [medline]
PHST- 2014/11/01 00:00 [pmc-release]
AID - IAI.01226-13 [pii]
AID - 01226-13 [pii]
AID - 10.1128/IAI.01226-13 [doi]
PST - ppublish
SO  - Infect Immun. 2014 May;82(5):1914-20. doi: 10.1128/IAI.01226-13. Epub 2014 Feb 
      24.