PMID- 30007055
OWN - NLM
STAT- MEDLINE
DCOM- 20190107
LR  - 20190107
IS  - 2041-1014 (Electronic)
IS  - 2041-1006 (Linking)
VI  - 33
IP  - 5
DP  - 2018 Oct
TI  - Porphyromonas gingivalis inhibits M2 activation of macrophages by suppressing 
      alpha-ketoglutarate production in mice.
PG  - 388-395
LID - 10.1111/omi.12241 [doi]
AB  - Reprograming of metabolic pathways is critical in governing the polarization of 
      macrophages into classical proinflammatory M1 or alternative anti-inflammatory M2 
      phenotypes in metabolic diseases, such as diabetes. Porphyromonas gingivalis, a 
      keystone pathogen of periodontitis, causes an imbalance in M1/M2 activation, 
      resulting in a hyperinflammatory environment that promotes the pathogenesis of 
      periodontitis. However, whether P. gingivalis infection modulates metabolic 
      pathways to alter macrophage polarization remains unclear. Bone-marrow-derived 
      macrophages (BMDMs) were collected from 6-week-old female C57BL/6 mice and 
      stimulated with P. gingivalis, P. gingivalis-derived LPS or IL-4. Relative gene 
      expression and protein production were measured by quantitative real-time PCR, 
      RNA sequencing and western blotting. Colorimetric assays were also performed to 
      assess the amounts of alpha-ketoglutarate (alpha-KG) and succinate. P. gingivalis or 
      P. gingivalis-derived LPS-induced inflammatory responses enhanced M1 macrophages 
      and suppressed M2 macrophages, even in the presence of IL-4. P. gingivalis 
      inhibited Idh1/2 and Gpt1/2 mRNA expression, and increased Akgdh mRNA expression, 
      thus decreasing the ratio of alpha-KG/succinate. Supplementation of cell-permeable 
      dimethyl-alpha-KG dramatically restored M2 activation during P. gingivalis infection. 
      Our study suggests that P. gingivalis maintains a hyperinflammatory state by 
      suppressing the production of alpha-KG by M2 macrophages.
CI  - (c) 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Yu, S
AU  - Yu S
AUID- ORCID: 0000-0003-1946-9151
AD  - School of Stomatology, Weifang Medical University, Weifang, China.
AD  - Clinical Research Center, Shanghai Jiading Central Hospital, Shanghai, China.
FAU - Ding, L
AU  - Ding L
AD  - School of Stomatology, Weifang Medical University, Weifang, China.
AD  - Clinical Research Center, Shanghai Jiading Central Hospital, Shanghai, China.
FAU - Liang, D
AU  - Liang D
AD  - Clinical Research Center, Shanghai Jiading Central Hospital, Shanghai, China.
FAU - Luo, L
AU  - Luo L
AD  - Department of Periodontics, The Affiliated Stomatology Hospital, Tongji 
      University, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180819
PL  - Denmark
TA  - Mol Oral Microbiol
JT  - Molecular oral microbiology
JID - 101524770
RN  - 0 (Ketoglutaric Acids)
RN  - 207137-56-2 (Interleukin-4)
MH  - Animals
MH  - Female
MH  - Interleukin-4/pharmacology
MH  - Ketoglutaric Acids/*metabolism
MH  - *Macrophage Activation
MH  - Macrophages/metabolism/*microbiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Periodontitis/microbiology
MH  - Porphyromonas gingivalis/genetics/*pathogenicity
MH  - Sequence Analysis, RNA
OTO - NOTNLM
OT  - Porphyromonas gingivalis
OT  - macrophage polarization
OT  - periodontitis
OT  - alpha-ketoglutarate
EDAT- 2018/07/15 06:00
MHDA- 2019/01/08 06:00
CRDT- 2018/07/15 06:00
PHST- 2018/07/12 00:00 [accepted]
PHST- 2018/07/15 06:00 [pubmed]
PHST- 2019/01/08 06:00 [medline]
PHST- 2018/07/15 06:00 [entrez]
AID - 10.1111/omi.12241 [doi]
PST - ppublish
SO  - Mol Oral Microbiol. 2018 Oct;33(5):388-395. doi: 10.1111/omi.12241. Epub 2018 Aug 
      19.