PMID- 31400857
OWN - NLM
STAT- MEDLINE
DCOM- 20200615
LR  - 20211204
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 517
IP  - 4
DP  - 2019 Oct 1
TI  - Sting is a critical regulator of spinal cord injury by regulating microglial 
      inflammation via interacting with TBK1 in mice.
PG  - 741-748
LID - S0006-291X(19)31499-8 [pii]
LID - 10.1016/j.bbrc.2019.07.125 [doi]
AB  - Spinal cord injury (SCI) is a devastating neurological condition that results in 
      progressive tissue loss, secondary to vascular dysfunction and inflammation. Lack 
      of effective pharmacotherapies for SCI is mainly attributable to an incomplete 
      understanding of its pathogenesis. Stimulator of interferon gene (Sting), also 
      known as Transmembrane protein 173 (TMEM173), activates the type I 
      interferon-regulated innate immune response, playing crucial role in modulating 
      inflammation. However, the mechanism underlying Sting activation in SCI is still 
      unclear. Here, we reported that Sting functioned as a positive regulator of SCI. 
      Sting expression was increased in the injured spinal cord samples of SCI mice, 
      along with significantly up-regulated levels of pro-inflammatory cytokines 
      including tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta and IL-6. 
      Suppressing Sting expression in lipopolysaccharide-incubated mouse microglia 
      markedly reduced the activation of nuclear factor-kappaB (NF-kappaB) and mitogen 
      activated protein kinases (MAPKs) signaling pathways, as illustrated by the 
      decreased phosphorylation of IKKbeta, IkappaBalpha, NF-kappaB/p65, p38, ERK1/2 and JNK. 
      Furthermore, LPS-stimulated release of pro-inflammatory cytokines in microglial 
      cells was also reversed by Sting knockdown. In contrast, LPS-induced inflammation 
      was further accelerated in microglial cells with Sting over-expression through 
      potentiating NF-kappaB and MAPKs signaling. Mechanistically, Sting directly 
      interacted with the TANK-binding kinase 1 (TBK1), thus promoting its 
      phosphorylation and the activation of down-streaming NF-kappaB and MAPKs signaling 
      pathways. Notably, the effects of Sting on SCI progression were verified in mice. 
      Consistently, Sting knockout alleviated inflammatory response and facilitated 
      recovery after SPI in mice through blocking TBK1 activation and subsequent NF-kappaB 
      and MAPKs phosphorylation. In summary, our findings may provide a novel strategy 
      for prevention and treatment of SCI by targeting Sting.
CI  - Copyright (c) 2019. Published by Elsevier Inc.
FAU - Wang, Yue-Yi
AU  - Wang YY
AD  - Second Department of Orthopaed, Ningbo Fenghua District Hospital of Traditional 
      Chinese Medicine, Ningbo, 315040, China. Electronic address: longhs121@qq.com.
FAU - Shen, Dong
AU  - Shen D
AD  - Second Department of Orthopaed, Ningbo Fenghua District Hospital of Traditional 
      Chinese Medicine, Ningbo, 315040, China.
FAU - Zhao, Liu-Jun
AU  - Zhao LJ
AD  - Department of Spine Surgery, Ningbo Sixth Hospital, Ningbo, 315040, China.
FAU - Zeng, Nian
AU  - Zeng N
AD  - Second Department of Orthopaed, Ningbo Fenghua District Hospital of Traditional 
      Chinese Medicine, Ningbo, 315040, China.
FAU - Hu, Teng-Hui
AU  - Hu TH
AD  - Second Department of Orthopaed, Ningbo Fenghua District Hospital of Traditional 
      Chinese Medicine, Ningbo, 315040, China.
LA  - eng
PT  - Journal Article
DEP - 20190807
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Sting1 protein, mouse)
RN  - EC 2.7.1.- (Tbk1 protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cytokines/metabolism
MH  - Enzyme Activation
MH  - Inflammation/*metabolism/*pathology
MH  - Inflammation Mediators
MH  - Lipopolysaccharides
MH  - MAP Kinase Signaling System/drug effects
MH  - Male
MH  - Membrane Proteins/*metabolism
MH  - Mice, Inbred C57BL
MH  - Microglia/*metabolism/*pathology
MH  - NF-kappa B/metabolism
MH  - Protein Binding
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Spinal Cord Injuries/*metabolism/*pathology
OTO - NOTNLM
OT  - Inflammation
OT  - NF-kappaB and MAPKs
OT  - Spinal cord injury (SCI)
OT  - Sting
OT  - TBK1
EDAT- 2019/08/12 06:00
MHDA- 2020/06/17 06:00
CRDT- 2019/08/12 06:00
PHST- 2019/07/23 00:00 [received]
PHST- 2019/07/31 00:00 [accepted]
PHST- 2019/08/12 06:00 [pubmed]
PHST- 2020/06/17 06:00 [medline]
PHST- 2019/08/12 06:00 [entrez]
AID - S0006-291X(19)31499-8 [pii]
AID - 10.1016/j.bbrc.2019.07.125 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2019 Oct 1;517(4):741-748. doi: 
      10.1016/j.bbrc.2019.07.125. Epub 2019 Aug 7.