PMID- 34992737
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220429
IS  - 2000-2297 (Print)
IS  - 2000-2297 (Electronic)
IS  - 2000-2297 (Linking)
VI  - 14
IP  - 1
DP  - 2022
TI  - Microtubule affinity regulating kinase 4 promoted activation of the NLRP3 
      inflammasome-mediated pyroptosis in periodontitis.
PG  - 2015130
LID - 10.1080/20002297.2021.2015130 [doi]
LID - 2015130
AB  - BACKGROUND: Microtubule dynamics plays a crucial role in the spatial arrangement 
      of cell organelles and activation of the NLRP3 inflammasome. PURPOSE: This study 
      aimed to explore whether microtubule affinity regulating kinase 4 (MARK4) can be 
      a therapeutic target of periodontitis by affecting microtubule dynamics and NLRP3 
      inflammasome-mediated pyroptosis in macrophages. MATERIALS AND METHODS: The NLRP3 
      inflammasome-related genes and MARK4 were measured in the healthy and inflamed 
      human gingival tissues. Bone marrow-derived macrophages (BMDMs) were infected 
      with Porphyromonas gingivalis, while the MARK4 inhibitors (OTSSP167 and Compound 
      50) and small interference RNA were utilized to restrain MARK4. 
      Apoptosis-associated speck-like protein (ASC) speck was detected by confocal, and 
      levels of interleukin-1beta (IL-1beta), as well as IL-18, were assessed by ELISA. 
      RESULTS: Increased staining and transcription of MARK4, NLRP3, ASC, and Caspase-1 
      were observed in the inflamed gingiva. P. gingivalis infection promoted MARK4 
      expression and the NLRP3 inflammasome in BMDMs. Inhibition of MARK4 decreased LDH 
      release, IL-1beta and IL-18 production, ASC speck formation, and the 
      pyroptosis-related genes transcription. Furthermore, MARK4 inhibition reduced 
      microtubule polymerization and acetylation in P. gingivalis-infected BMDMs. 
      CONCLUSIONS: MARK4 promoted NLRP3 inflammasome activation and pyroptosis in P. 
      gingivalis-infected BMDMs by affecting microtubule dynamics. MARK4 inhibition 
      might be a potential target in regulating the NLRP3 inflammasome during 
      periodontitis progress.
CI  - (c) 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & 
      Francis Group.
FAU - Wang, Lulu
AU  - Wang L
AUID- ORCID: 0000-0002-7279-3770
AD  - Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, 
      China.
AD  - Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical 
      School of Nanjing University, Nanjing, China.
FAU - Pu, Wenchen
AU  - Pu W
AUID- ORCID: 0000-0003-0929-9566
AD  - Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China.
AD  - Laboratory of Molecular Oncology, Frontiers Science Center for Disease-related 
      Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West 
      China Hospital, Sichuan University, Chengdu, China.
FAU - Wang, Chun
AU  - Wang C
AD  - Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China.
FAU - Lei, Lang
AU  - Lei L
AUID- ORCID: 0000-0003-2892-040X
AD  - Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, 
      China.
FAU - Li, Houxuan
AU  - Li H
AUID- ORCID: 0000-0002-3798-8628
AD  - Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20211227
PL  - United States
TA  - J Oral Microbiol
JT  - Journal of oral microbiology
JID - 101551049
PMC - PMC8725745
OTO - NOTNLM
OT  - MARK4
OT  - NLRP3 inflammasome
OT  - Porphyromonas gingivalis
OT  - periodontitis
OT  - pyroptosis
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2022/01/08 06:00
MHDA- 2022/01/08 06:01
PMCR- 2021/12/27
CRDT- 2022/01/07 06:24
PHST- 2022/01/07 06:24 [entrez]
PHST- 2022/01/08 06:00 [pubmed]
PHST- 2022/01/08 06:01 [medline]
PHST- 2021/12/27 00:00 [pmc-release]
AID - 2015130 [pii]
AID - 10.1080/20002297.2021.2015130 [doi]
PST - epublish
SO  - J Oral Microbiol. 2021 Dec 27;14(1):2015130. doi: 10.1080/20002297.2021.2015130. 
      eCollection 2022.