PMID- 34268368
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220424
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 9
IP  - 9
DP  - 2021 May
TI  - PRMT5 inhibition modulates murine dendritic cells activation by inhibiting the 
      metabolism switch: a new therapeutic target in periodontitis.
PG  - 755
LID - 10.21037/atm-20-7362 [doi]
LID - 755
AB  - BACKGROUND: Protein arginine methyltransferase 5 (PRMT5) catalyzes the 
      methylation of arginine residues in multiple proteins. Recent reports have 
      highlighted the anti-inflammatory role of PRMT5. Dendritic cells (DCs) are 
      well-known professional antigen-presenting cells that are crucial for immune 
      response initiation. However, whether PRMT5 participates in DC immunity processes 
      is unknown. METHODS: In an in vitro experiment, a PRMT5 inhibitor (EPZ015666) was 
      used to inhibit PRMT5 expression, and lipopolysaccharide (LPS) stimulation was 
      applied to mimic the inflammation context. Proinflammatory cytokine production, 
      interferon-stimulated genes (ISGs), costimulatory molecules, major 
      histocompatibility complex (MHC) expression and DC metabolism were measured 
      following PRMT5 inhibition and LPS stimulation. In an in vivo study, we first 
      tested PRMT5 mRNA and protein expression in a BALB/c mouse ligature-induced 
      periodontitis model. Then, we evaluated changes in periodontal tissue and DC 
      migration to cervical lymph nodes after local treatment with the PRMT5 inhibitor. 
      RESULTS: The in vitro results revealed that PRMT5 inhibition attenuated DC 
      activation and maturation by inhibiting the expression of proinflammatory 
      cytokines, ISGs, costimulatory molecules, and MHC induced by LPS stimulation. We 
      also found that inhibition of PRMT5 blocked the DC metabolic switch to 
      glycolysis. In the in vivo study, we found that PRMT5 inhibition reversed the 
      severity of the lesions and slowed the migration of DCs to cervical lymph nodes. 
      CONCLUSIONS: The results show a critical role of PRMT5 in the control of DC 
      activation through inhibition of the metabolic switch and indicate that PRMT5 is 
      a promising therapeutic target in periodontitis.
CI  - 2021 Annals of Translational Medicine. All rights reserved.
FAU - Mi, Wenxiang
AU  - Mi W
AD  - Department of Implant Dentistry, Shanghai Ninth People's Hospital, College of 
      Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical 
      Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology & 
      Shanghai Research Institute of Stomatology, Shanghai, China.
AD  - Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's 
      Hospital Research Center, Shanghai Jiao Tong University School of Medicine, 
      Shanghai, China.
FAU - Qiao, Shichong
AU  - Qiao S
AD  - Department of Implant Dentistry, Shanghai Ninth People's Hospital, College of 
      Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical 
      Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology & 
      Shanghai Research Institute of Stomatology, Shanghai, China.
FAU - Zhang, Xiaomeng
AU  - Zhang X
AD  - Department of Implant Dentistry, Shanghai Ninth People's Hospital, College of 
      Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical 
      Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology & 
      Shanghai Research Institute of Stomatology, Shanghai, China.
FAU - Wu, Dongle
AU  - Wu D
AD  - Department of Implant Dentistry, Shanghai Ninth People's Hospital, College of 
      Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical 
      Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology & 
      Shanghai Research Institute of Stomatology, Shanghai, China.
FAU - Zhou, Linyi
AU  - Zhou L
AD  - Department of Implant Dentistry, Shanghai Ninth People's Hospital, College of 
      Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical 
      Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology & 
      Shanghai Research Institute of Stomatology, Shanghai, China.
FAU - Lai, Hongchang
AU  - Lai H
AD  - Department of Implant Dentistry, Shanghai Ninth People's Hospital, College of 
      Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical 
      Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology & 
      Shanghai Research Institute of Stomatology, Shanghai, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC8246170
OTO - NOTNLM
OT  - Dendritic cells (DCs)
OT  - immunity
OT  - inflammation
OT  - metabolism
OT  - periodontitis
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at http://dx.doi.org/10.21037/atm-20-7362). The authors have no 
      conflicts of interest to declare.
EDAT- 2021/07/17 06:00
MHDA- 2021/07/17 06:01
PMCR- 2021/05/01
CRDT- 2021/07/16 06:42
PHST- 2020/11/09 00:00 [received]
PHST- 2021/03/05 00:00 [accepted]
PHST- 2021/07/16 06:42 [entrez]
PHST- 2021/07/17 06:00 [pubmed]
PHST- 2021/07/17 06:01 [medline]
PHST- 2021/05/01 00:00 [pmc-release]
AID - atm-09-09-755 [pii]
AID - 10.21037/atm-20-7362 [doi]
PST - ppublish
SO  - Ann Transl Med. 2021 May;9(9):755. doi: 10.21037/atm-20-7362.