PMID- 33588175
OWN - NLM
STAT- MEDLINE
DCOM- 20210609
LR  - 20210609
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 94
DP  - 2021 May
TI  - Hypoxia and Porphyromonas gingivalis-lipopolysaccharide synergistically induce 
      NLRP3 inflammasome activation in human gingival fibroblasts.
PG  - 107456
LID - S1567-5769(21)00092-8 [pii]
LID - 10.1016/j.intimp.2021.107456 [doi]
AB  - OBJECTIVE: To investigate the effects of hypoxia and Porphyromonas gingivalis- 
      lipopolysaccharide (P. gingivalis-LPS) on activation of the NACHT leucine-rich 
      repeat protein 3 (NLRP3) inflammasome in human gingival fibroblasts (HGFs). 
      DESIGN: Periodontitis was optimally simulated using a hypoxic concentration of 
      1%. HGFs were stimulated using P. gingivalis-LPS (1.0 mug/ml) in normoxia and 
      hypoxia for 3 h and 6 h, respectively. The expression levels of genes and 
      proteins of hypoxia-inducible factor-1alpha (HIF-1alpha), interleukin-1beta, gasdermin D 
      (GSDMD) and the NLRP3 inflammasome, including NLRP3, apoptosis-associated 
      speck-like protein containing CARD (ASC), caspase-1 and its activated forms, were 
      measured using quantitative real-time polymerase chain reaction and western blot. 
      ELISA was used to detect and determine levels of the inflammatory factor 
      interleukin-1beta in cell supernatants. Lactate dehydrogenase (LDH) release assay, 
      caspase-1 activity assay and Hoechst 33342/Propidium Iodide (PI) staining were 
      performed to further verify the presence of pyroptosis. RESULTS: The NLRP3 
      inflammasome (i.e., NLRP3, ASC, caspase-1) was not affected by individual 
      stimulation using P. gingivalis-LPS or hypoxia. However, the combination of both 
      hypoxia and P. gingivalis-LPS stimulation significantly enhanced inflammasome 
      activation and promoted the expression of interleukin-1beta, gasdermin D and HIF-1alpha 
      at gene and protein levels; PI positive cells and the release of LDH were also 
      elevated. CONCLUSION: Hypoxia and P. gingivalis-LPS synergistically induced NLRP3 
      inflammasome activation in HGFs, and subsequently high levels of interleukin-1beta 
      and GSDMD-mediated pyroptosis can cause an HGF inflammatory response, which plays 
      an important role in the pathogenesis of periodontitis.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Yang, Kai
AU  - Yang K
AD  - Department of Periodontology, The Affiliated Hospital of Qingdao University, 
      Qingdao, Shandong, China; School of Stomatology, Qingdao University, Qingdao, 
      Shandong, China.
FAU - Xu, Shuo
AU  - Xu S
AD  - Laboratory of Oral Microbiology, Shanghai Research Institute of Stomatology, 
      Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 
      Shanghai, China.
FAU - Zhao, Hongmei
AU  - Zhao H
AD  - Department of Prosthodontics, The Affiliated Hospital of Qingdao University, 
      Qingdao, Shandong, China.
FAU - Liu, Lingshuang
AU  - Liu L
AD  - Department of Endodontics, The Affiliated Hospital of Qingdao University, 
      Qingdao, Shandong, China.
FAU - Lv, Xiaofang
AU  - Lv X
AD  - Department of Periodontology, The Affiliated Hospital of Qingdao University, 
      Qingdao, Shandong, China; School of Stomatology, Qingdao University, Qingdao, 
      Shandong, China.
FAU - Hu, Fang
AU  - Hu F
AD  - Department of Periodontology, The Affiliated Hospital of Qingdao University, 
      Qingdao, Shandong, China; School of Stomatology, Qingdao University, Qingdao, 
      Shandong, China.
FAU - Wang, Lei
AU  - Wang L
AD  - Department of Periodontology, The Affiliated Hospital of Qingdao University, 
      Qingdao, Shandong, China; School of Stomatology, Qingdao University, Qingdao, 
      Shandong, China.
FAU - Ji, Qiuxia
AU  - Ji Q
AD  - Department of Periodontology, The Affiliated Hospital of Qingdao University, 
      Qingdao, Shandong, China; School of Stomatology, Qingdao University, Qingdao, 
      Shandong, China. Electronic address: jqx_1@163.com.
LA  - eng
PT  - Journal Article
DEP - 20210212
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (GSDMD protein, human)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (IL1B protein, human)
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (NLRP3 protein, human)
RN  - 0 (Phosphate-Binding Proteins)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Cell Hypoxia/*immunology
MH  - Female
MH  - Fibroblasts/*immunology
MH  - Gingiva/cytology
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/immunology
MH  - Inflammasomes/genetics/*immunology
MH  - Interleukin-1beta/genetics/immunology
MH  - Intracellular Signaling Peptides and Proteins/genetics/immunology
MH  - *Lipopolysaccharides
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/genetics/*immunology
MH  - Phosphate-Binding Proteins/genetics/immunology
MH  - *Porphyromonas gingivalis
MH  - Young Adult
OTO - NOTNLM
OT  - HIF-1alpha
OT  - Hypoxia
OT  - IL-1beta
OT  - NLRP3 inflammasome
OT  - P. gingivalis-LPS
OT  - Periodontitis
EDAT- 2021/02/16 06:00
MHDA- 2021/06/10 06:00
CRDT- 2021/02/15 20:12
PHST- 2020/09/06 00:00 [received]
PHST- 2021/01/13 00:00 [revised]
PHST- 2021/01/28 00:00 [accepted]
PHST- 2021/02/16 06:00 [pubmed]
PHST- 2021/06/10 06:00 [medline]
PHST- 2021/02/15 20:12 [entrez]
AID - S1567-5769(21)00092-8 [pii]
AID - 10.1016/j.intimp.2021.107456 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2021 May;94:107456. doi: 10.1016/j.intimp.2021.107456. Epub 
      2021 Feb 12.