PMID- 35954253
OWN - NLM
STAT- MEDLINE
DCOM- 20220815
LR  - 20221106
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 11
IP  - 15
DP  - 2022 Aug 4
TI  - Cytosolic HMGB1 Mediates LPS-Induced Autophagy in Microglia by Interacting with 
      NOD2 and Suppresses Its Proinflammatory Function.
LID - 10.3390/cells11152410 [doi]
LID - 2410
AB  - The high mobility group box 1 (HMGB1), a well-known danger-associated molecule 
      pattern (DAMP) molecule, is a non-histone chromosomal protein localized in the 
      nucleus under normal physiological conditions. HMGB1 exhibits diverse functions 
      depending on its subcellular location. In the present study, we investigated the 
      role of HMGB1-induced autophagy in the lipopolysaccharide (LPS)-treated BV2 
      microglial cell line in mediating the transition between the inflammatory and 
      autophagic function of the nucleotide-binding oligomerization domain-containing 2 
      (NOD2), a cytoplasmic pattern-recognition receptor. The induction of the 
      microtubule-associated protein 1 light chain 3 (LC3), an autophagy biomarker, was 
      detected slowly in BV2 cells after the LPS treatment, and peak induction was 
      detected at 12 h. Under these conditions, NOD2 level was significantly increased 
      and the binding between HMGB1 and NOD2 and between HMGB1 and ATG16L1 was markedly 
      enhanced and the temporal profiles of the LC3II induction and HMGB1-NOD2 and 
      HMGB1-ATG16L1 complex formation coincided with the cytosolic accumulation of 
      HMGB1. The LPS-mediated autophagy induction was significantly suppressed in BV2 
      cells after HMGB1 or NOD2 knock-down (KD), indicating that HMGB1 contributes to 
      NOD2-mediated autophagy induction in microglia. Moreover, NOD2-RIP2 
      interaction-mediated pro-inflammatory cytokine induction and NF-kappaB activity were 
      significantly enhanced in BV2 cells after HMGB1 KD, indicating that HMGB1 plays a 
      critical role in the modulation of NOD2 function between pro-inflammation and 
      pro-autophagy in microglia. The effects of the cell-autonomous pro-autophagic 
      pathway operated by cytoplasmic HMGB1 may be beneficial, whereas those from the 
      paracrine pro-inflammatory pathway executed by extracellularly secreted HMGB1 can 
      be detrimental. Thus, the overall functional significance of HMGB1-induced 
      autophagy is different, depending on its temporal activity.
FAU - Kim, Seung-Woo
AU  - Kim SW
AD  - Department of Biomedical Sciences, Inha University School of Medicine, Inchon 
      22212, Korea.
FAU - Oh, Sang-A
AU  - Oh SA
AD  - Department of Anatomy, Inha University School of Medicine, Incheon 22212, Korea.
FAU - Seol, Song-I
AU  - Seol SI
AD  - Department of Anatomy, Inha University School of Medicine, Incheon 22212, Korea.
FAU - Davaanyam, Dashdulam
AU  - Davaanyam D
AD  - Department of Anatomy, Inha University School of Medicine, Incheon 22212, Korea.
FAU - Lee, Ja-Kyeong
AU  - Lee JK
AD  - Department of Anatomy, Inha University School of Medicine, Incheon 22212, Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220804
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Alarmins)
RN  - 0 (HMGB1 Protein)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
SB  - IM
MH  - Alarmins/metabolism
MH  - Autophagy
MH  - *HMGB1 Protein/metabolism
MH  - Lipopolysaccharides/metabolism/pharmacology
MH  - *Microglia/metabolism
MH  - NF-kappa B/metabolism
PMC - PMC9368039
OTO - NOTNLM
OT  - HMGB1
OT  - NOD2
OT  - autophagy
OT  - inflammation
OT  - microglia
COIS- The authors declare that they have no conflict of interest.
EDAT- 2022/08/13 06:00
MHDA- 2022/08/16 06:00
PMCR- 2022/08/04
CRDT- 2022/08/12 01:04
PHST- 2022/06/23 00:00 [received]
PHST- 2022/07/26 00:00 [revised]
PHST- 2022/08/02 00:00 [accepted]
PHST- 2022/08/12 01:04 [entrez]
PHST- 2022/08/13 06:00 [pubmed]
PHST- 2022/08/16 06:00 [medline]
PHST- 2022/08/04 00:00 [pmc-release]
AID - cells11152410 [pii]
AID - cells-11-02410 [pii]
AID - 10.3390/cells11152410 [doi]
PST - epublish
SO  - Cells. 2022 Aug 4;11(15):2410. doi: 10.3390/cells11152410.