PMID- 33879372
OWN - NLM
STAT- MEDLINE
DCOM- 20220303
LR  - 20220531
IS  - 1879-1409 (Electronic)
IS  - 0305-4179 (Linking)
VI  - 48
IP  - 1
DP  - 2022 Feb
TI  - The cGAS-STING pathway connects mitochondrial damage to inflammation in 
      burn-induced acute lung injury in rat.
PG  - 168-175
LID - S0305-4179(21)00088-7 [pii]
LID - 10.1016/j.burns.2021.04.007 [doi]
AB  - OBJECTIVE: Damage associated molecular patterns (DAMPs) are pathological 
      mediators linking local tissue damage to systemic inflammation in various 
      diseases. Some DAMPs, such as mitochondrial DNA (mtDNA), can be recognized by the 
      cytoplasmic cGAS protein to trigger the activation of the stimulator of 
      interferon genes (STING)-dependent innate immune pathway responsible for 
      infection or sterile inflammation. The objective of our study was to evaluate the 
      association between circulating mtDNA and cGAS-STING pathway activation in 
      mediating inflammation following burn injury. METHODS: 48 adult Sprague-Dawley 
      male rats were divided into eight groups (Sham, 2, 4, 8, 12, 24, 48, 72 h after 
      burn injury). The animals underwent 40% total body surface area scald injury to 
      produce a full-thickness burn. Plasma samples were collected via cardiac puncture 
      under deep anesthesia. Tissues were harvested and placed in formalin, followed by 
      paraffin embedment. Total plasma DNA was isolated followed by measurement of 
      mtDNA using quantitative polymerase chain reaction. Haemotoxylin-Eosin stain and 
      Western blot was used for lung histology and protein assays, respectively. 
      Statistical analyses were performed using ANOVA and student's t-test and 
      represented as mean +/- s.d. RESULTS: Plasma mtDNA trended upward at early 
      time-points following burn injury with peak levels at 8 h after burn when 
      compared to the control group (345 +/- 83.4 copies/mul vs. 239 +/- 43.1 copies/mul, p = 
      0.07) and followed a bell-shaped distribution. Lung slices from burned rats 
      showed acute injury marked by increased inflammatory infiltrate, with the maximum 
      changes seen at 24 h, accompanied with significant upregulation of neutrophil 
      elastase (p = 0.04). Compared with sham animals, cGAS and STING protein levels in 
      lung tissue were up-regulated at 4 and 8 h after burn (p = 0.03 and p < 0.001, 
      respectively). CONCLUSION: Activation of the cGAS-STING pathway by increased 
      plasma mtDNA is an important pathway driving neutrophil infiltration in 
      burn-induced acute lung injury in rats. A further understanding of the 
      STING-mediated immunopathology in lung and other susceptible organs may be 
      important for the development of novel therapies for burn injury.
CI  - Copyright (c) 2021 Elsevier Ltd and ISBI. All rights reserved.
FAU - Comish, Paul B
AU  - Comish PB
AD  - Department of Surgery, University of Texas Southwestern, Dallas, TX, USA. 
      Electronic address: Paul.Comish@UTSouthwestern.edu.
FAU - Liu, Ming-Mei
AU  - Liu MM
AD  - Department of Surgery, University of Texas Southwestern, Dallas, TX, USA.
FAU - Huebinger, Ryan
AU  - Huebinger R
AD  - Department of Surgery, University of Texas Southwestern, Dallas, TX, USA.
FAU - Carlson, Deborah
AU  - Carlson D
AD  - Department of Surgery, University of Texas Southwestern, Dallas, TX, USA.
FAU - Kang, Rui
AU  - Kang R
AD  - Department of Surgery, University of Texas Southwestern, Dallas, TX, USA.
FAU - Tang, Daolin
AU  - Tang D
AD  - Department of Surgery, University of Texas Southwestern, Dallas, TX, USA. 
      Electronic address: daolin.tang@utsouthwestern.edu.
LA  - eng
GR  - R01 GM115366/GM/NIGMS NIH HHS/United States
GR  - R01 GM127791/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20210418
PL  - Netherlands
TA  - Burns
JT  - Burns : journal of the International Society for Burn Injuries
JID - 8913178
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Membrane Proteins)
RN  - 0 (Sting1 protein, rat)
RN  - EC 2.7.7.- (Cgas protein, rat)
RN  - EC 2.7.7.- (Nucleotidyltransferases)
SB  - IM
MH  - *Acute Lung Injury/complications
MH  - *Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - *Burns/complications
MH  - Inflammation/metabolism
MH  - Male
MH  - *Membrane Proteins
MH  - *Nucleotidyltransferases/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
OTO - NOTNLM
OT  - Burn injury
OT  - DAMP
OT  - Innate immune
OT  - Lung
OT  - Mitochondrial DNA
OT  - STING
OT  - cGAS
EDAT- 2021/04/22 06:00
MHDA- 2022/03/04 06:00
CRDT- 2021/04/21 05:50
PHST- 2020/06/18 00:00 [received]
PHST- 2021/03/22 00:00 [revised]
PHST- 2021/04/06 00:00 [accepted]
PHST- 2021/04/22 06:00 [pubmed]
PHST- 2022/03/04 06:00 [medline]
PHST- 2021/04/21 05:50 [entrez]
AID - S0305-4179(21)00088-7 [pii]
AID - 10.1016/j.burns.2021.04.007 [doi]
PST - ppublish
SO  - Burns. 2022 Feb;48(1):168-175. doi: 10.1016/j.burns.2021.04.007. Epub 2021 Apr 
      18.