PMID- 35075953
OWN - NLM
STAT- MEDLINE
DCOM- 20230418
LR  - 20230420
IS  - 1521-0499 (Electronic)
IS  - 0190-2148 (Linking)
VI  - 48
IP  - 2
DP  - 2022 Feb-Mar
TI  - Cell cycle kinase CHEK2 in macrophages alleviates the inflammatory response to 
      Staphylococcus aureus-induced pneumonia.
PG  - 53-60
LID - 10.1080/01902148.2022.2029625 [doi]
AB  - BACKGROUND: Excessive macrophage-mediated inflammation participates in the 
      development of Staphylococcus aureus (S. aureus)-induced pneumonia. Checkpoint 
      kinase 2 (Chek2) was screened out as macrophage-related infantile pneumonia gene 
      after the differentially expressed analysis of RNAseq data derived from pam3CSK4 
      stimulated bone marrow-derived macrophages (BMDMs). METHODS: RAW264.7 macrophage 
      cells were transfected with Chek2-specific gRNA, which were further overexpressed 
      with wide-type Chek2 or Chek2 kinase activity mutant (Chek2 KD, D368N). At the 
      same time, the relative protein and mRNA expression of inflammatory cytokines 
      were determined. C57BL/6J WT mice were intranasally infected with S. aureus to 
      induce S. aureus-induced pneumonia, which was treated with BML-277, an inhibitor 
      of Chek2. The symptoms of pneumonia mice and inflammatory cytokines associated 
      with the nuclear factor kappa B (NF-kappaB) signaling pathways were further examined. 
      RESULTS: In vivo, BML-277 significantly promoted pneumonia symptoms, including 
      mortality, lung infiltration of immune cells, and the abundance of lung 
      pro-inflammatory cytokines. Mechanically, BML-277 did not affect BMDMs survival 
      but up-regulated the mRNA expression of tumor necrosis factor (Tnf), nitric oxide 
      synthase 2 (Nos2), interleukin (Il)23a, and the secretion of Tnf-alpha and Il-23a. At 
      the same time, genetic complementation experiment testified that Chek2 KD did not 
      inhibit NF-kappaB and relevant inflammatory cytokines expression. CONCLUSION: Chek2 
      functions through the kinase mechanism to down-regulate the NF-kappaB pathway in 
      macrophages to alleviate S. aureus-induced pneumonia in mice.
FAU - Xie, Fei
AU  - Xie F
AD  - Department of Pediatrics, Cangzhou Central Hospital, Cangzhou, Hebei, China.
FAU - Chen, Ruidong
AU  - Chen R
AD  - Department of Pediatrics, Cangzhou Central Hospital, Cangzhou, Hebei, China.
FAU - Zhao, Jie
AU  - Zhao J
AD  - Department of Pediatrics, Cangzhou Central Hospital, Cangzhou, Hebei, China.
FAU - Xu, Chunyan
AU  - Xu C
AD  - Department of Pediatrics, Cangzhou Central Hospital, Cangzhou, Hebei, China.
FAU - Zan, Chunxiang
AU  - Zan C
AD  - Child Healthcare Department, Cangzhou Central Hospital, Cangzhou, Hebei, China.
FAU - Yue, Bin
AU  - Yue B
AD  - Department of Pediatrics, Cangzhou Central Hospital, Cangzhou, Hebei, China.
FAU - Tian, Wenqiu
AU  - Tian W
AD  - Department of Pediatrics, Cangzhou Central Hospital, Cangzhou, Hebei, China.
FAU - Yi, Wenxia
AU  - Yi W
AD  - Department of Pediatrics, Cangzhou Central Hospital, Cangzhou, Hebei, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220125
PL  - England
TA  - Exp Lung Res
JT  - Experimental lung research
JID - 8004944
RN  - 0 (NF-kappa B)
RN  - EC 2.7.1.11 (Checkpoint Kinase 2)
RN  - 0 (Cytokines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (RNA, Messenger)
RN  - 0 (Lipopolysaccharides)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *NF-kappa B/metabolism
MH  - Staphylococcus aureus
MH  - Checkpoint Kinase 2/metabolism
MH  - Mice, Inbred C57BL
MH  - Macrophages/metabolism
MH  - Cytokines/metabolism
MH  - *Pneumonia/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Cell Cycle
MH  - RNA, Messenger/metabolism
MH  - Lipopolysaccharides/pharmacology
OTO - NOTNLM
OT  - CHEK2
OT  - NF-kappaB
OT  - Nos2
OT  - macrophages
OT  - pneumonia
EDAT- 2022/01/26 06:00
MHDA- 2023/04/18 06:41
CRDT- 2022/01/25 08:46
PHST- 2023/04/18 06:41 [medline]
PHST- 2022/01/26 06:00 [pubmed]
PHST- 2022/01/25 08:46 [entrez]
AID - 10.1080/01902148.2022.2029625 [doi]
PST - ppublish
SO  - Exp Lung Res. 2022 Feb-Mar;48(2):53-60. doi: 10.1080/01902148.2022.2029625. Epub 
      2022 Jan 25.