PMID- 37686068
OWN - NLM
STAT- MEDLINE
DCOM- 20230911
LR  - 20230915
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 17
DP  - 2023 Aug 26
TI  - NLRC5 Deficiency Reduces LPS-Induced Microglial Activation via Inhibition of 
      NF-kappaB Signaling and Ameliorates Mice's Depressive-like Behavior.
LID - 10.3390/ijms241713265 [doi]
LID - 13265
AB  - Microglia are believed to be the key immune effectors of the central immune 
      microenvironment, and their dysregulation is associated with neuroinflammation 
      and mood disorders. Nucleotide-binding oligomerization domain-like receptor 
      family caspase recruitment domain-containing five (NLRC5) is a new member of the 
      Nod-like receptor family. Recently, NLRC5 has been reported to be expressed by 
      microglia. Nonetheless, the exact roles of NLRC5 in microglial activation and its 
      function in depression have not been investigated yet. Herein, we found that 
      reducing NLRC5 decreased lipopolysaccharide (LPS)-induced secretion of 
      pro-inflammatory cytokines (IL-1beta, IL-6, and TNF-alpha) in primary cultured microglia 
      and microglial cell lines but not in bone marrow-derived macrophages (BMDMs). In 
      more detail, reducing NLRC5 diminished the secretion of LPS-induced cytokines by 
      attenuating IKKalpha/beta phosphorylation and inhibiting NF-kappaB signaling. Moreover, the 
      expression of Nlrc5 in the hippocampus of LPS- or chronic unpredictable mild 
      stress (CUMS)-induced depressive mice was increased. In line with the in vitro 
      findings, Nlrc5 deficiency inhibited microglial activation in the mouse 
      hippocampus and improved LPS- or CUMS-induced depressive-like behaviors. In 
      summary, we demonstrated the critical role of NLRC5 in LPS-induced microglial 
      activation and LPS- or CUMS-induced depressive mouse models.
FAU - Sun, Chen
AU  - Sun C
AD  - Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of 
      Microbiology and Immunology, School of Medicine, Southeast University, Nanjing 
      210009, China.
FAU - Shen, Yuqing
AU  - Shen Y
AD  - Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of 
      Microbiology and Immunology, School of Medicine, Southeast University, Nanjing 
      210009, China.
FAU - Liu, Piaopiao
AU  - Liu P
AD  - Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, 
      Southeast University, Nanjing 210009, China.
FAU - Shen, Yi
AU  - Shen Y
AD  - Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, 
      Southeast University, Nanjing 210009, China.
FAU - Hu, Yue
AU  - Hu Y
AD  - Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, 
      Southeast University, Nanjing 210009, China.
FAU - Li, Ping
AU  - Li P
AD  - Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, 
      Southeast University, Nanjing 210009, China.
FAU - Zhang, Ying
AU  - Zhang Y
AD  - Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of 
      Microbiology and Immunology, School of Medicine, Southeast University, Nanjing 
      210009, China.
FAU - Miao, Fengqin
AU  - Miao F
AD  - Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, 
      Southeast University, Nanjing 210009, China.
FAU - Zhang, Jianqiong
AU  - Zhang J
AD  - Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of 
      Microbiology and Immunology, School of Medicine, Southeast University, Nanjing 
      210009, China.
AD  - Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, 
      Southeast University, Nanjing 210009, China.
LA  - eng
GR  - 2021ZD0204001/Scientific and technological innovation 2030 
      (STI2030)-Major-Projects of China/
PT  - Journal Article
DEP - 20230826
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (NF-kappa B)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Cytokines)
RN  - 0 (NLRC5 protein, mouse)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *NF-kappa B
MH  - *Lipopolysaccharides/toxicity
MH  - Microglia
MH  - Signal Transduction
MH  - Cytokines
MH  - Intracellular Signaling Peptides and Proteins/genetics
PMC - PMC10487775
OTO - NOTNLM
OT  - NF-kappaB
OT  - NLRC5
OT  - depressive mouse model
OT  - microglia
OT  - neuroinflammation
COIS- The authors declare that there is no conflict of interest regarding the 
      publication of this paper.
EDAT- 2023/09/09 11:44
MHDA- 2023/09/11 06:42
PMCR- 2023/08/26
CRDT- 2023/09/09 01:11
PHST- 2023/06/19 00:00 [received]
PHST- 2023/08/09 00:00 [revised]
PHST- 2023/08/23 00:00 [accepted]
PHST- 2023/09/11 06:42 [medline]
PHST- 2023/09/09 11:44 [pubmed]
PHST- 2023/09/09 01:11 [entrez]
PHST- 2023/08/26 00:00 [pmc-release]
AID - ijms241713265 [pii]
AID - ijms-24-13265 [pii]
AID - 10.3390/ijms241713265 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Aug 26;24(17):13265. doi: 10.3390/ijms241713265.