PMID- 37698122
OWN - NLM
STAT- MEDLINE
DCOM- 20231106
LR  - 20231106
IS  - 2058-7384 (Electronic)
IS  - 0394-6320 (Print)
IS  - 0394-6320 (Linking)
VI  - 37
DP  - 2023 Jan-Dec
TI  - Activation of GPR81 aggravated intestinal ischemia/reperfusion injury-induced 
      acute lung injury via HMGB1-mediated neutrophil extracellular traps formation.
PG  - 3946320231193832
LID - 10.1177/03946320231193832 [doi]
LID - 03946320231193832
AB  - INTRODUCTION: Intestinal ischemia/reperfusion (II/R) injury is a life-threatening 
      situation accompanied by severe organ injury, especially acute lung injury (ALI). 
      A great body of evidence indicates that II/R injury is usually associated with 
      hyperlactatemia. G-protein-coupled receptor 81 (GPR81), a receptor of lactate, 
      has been recognized as a regulatory factor in inflammation, but whether it was 
      involved in II/R injury-induced ALI is still unknown. METHODS: To establish the 
      II/R injury model, the superior mesenteric artery of the mice was occluded gently 
      by a microvascular clamp for 45 min to elicit intestinal ischemia and then a 
      90-min reperfusion was performed. Broncho-alveolar lavage fluid (BALF) and lung 
      tissues were obtained to evaluate the lung injury after II/R. The pulmonary 
      histopathological alteration was evaluated by H&E staining. The concentration of 
      proteins, the number of infiltrated cells, and the level of IL-6 were measured in 
      BALF. The formation of neutrophil extracellular traps (NETs) was evaluated by the 
      level of double-stranded DNA (dsDNA) and myeloperoxidase- double-stranded DNA 
      (MPO-dsDNA) complex in BALF, and the content of citrullinated histone H3 (Cit-H3) 
      in lung tissue. The level of HMGB1 in the BALF and plasma was measured by enzyme 
      linked immunosorbent assay (ELISA). RESULTS: Administration of the GPR81 agonist 
      3,5-dihydroxybenzoic acid (DHBA) aggravated II/R injury-induced lung histological 
      abnormalities, upregulated the concentration of proteins, the number of 
      infiltrated cells, and the level of IL-6 in BALF. In addition, DHBA treatment 
      increased the level of dsDNA and MPO-dsDNA complex in BALF, and promoted the 
      elevation of Cit-H3 in lung tissue and the release of HMGB1 in BALF and plasma. 
      CONCLUSION: After induction of ALI by II/R, the administration of DHBA aggravated 
      ALI through NETs formation in the lung.
FAU - Yili, Sun
AU  - Yili S
AD  - Department of Pathophysiology, Chongqing Medical University, Chongqing, China. 
      RINGGOLD: 12550
FAU - Xinyi, Dai
AU  - Xinyi D
AD  - Department of Pathophysiology, Chongqing Medical University, Chongqing, China. 
      RINGGOLD: 12550
FAU - Kerui, Fan
AU  - Kerui F
AD  - Department of Pathophysiology, Chongqing Medical University, Chongqing, China. 
      RINGGOLD: 12550
FAU - Kun, Chen
AU  - Kun C
AD  - Department of Pathophysiology, Chongqing Medical University, Chongqing, China. 
      RINGGOLD: 12550
FAU - Yang, Yongqiang
AU  - Yang Y
AUID- ORCID: 0000-0003-2048-8309
AD  - Department of Pathophysiology, Chongqing Medical University, Chongqing, China. 
      RINGGOLD: 12550
FAU - Zhang, Li
AU  - Zhang L
AD  - Department of Pathophysiology, Chongqing Medical University, Chongqing, China. 
      RINGGOLD: 12550
FAU - Hu, Kai
AU  - Hu K
AUID- ORCID: 0000-0001-6564-9845
AD  - Department of Histology and Embryology, Chongqing Medical University, Chongqing, 
      China. RINGGOLD: 12550
LA  - eng
PT  - Journal Article
PL  - England
TA  - Int J Immunopathol Pharmacol
JT  - International journal of immunopathology and pharmacology
JID - 8911335
RN  - 9007-49-2 (DNA)
RN  - 0 (HMGB1 Protein)
RN  - 0 (Interleukin-6)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (HMGB1 protein, human)
RN  - 0 (HCAR1 protein, human)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Acute Lung Injury/chemically induced
MH  - DNA/adverse effects/metabolism
MH  - *Extracellular Traps/metabolism
MH  - *HMGB1 Protein/metabolism
MH  - Interleukin-6/metabolism
MH  - Ischemia/complications/metabolism/pathology
MH  - Lung/pathology
MH  - Receptors, G-Protein-Coupled/metabolism
MH  - *Reperfusion Injury/metabolism
PMC - PMC10498694
OTO - NOTNLM
OT  - GPR81
OT  - acute lung injury
OT  - inflammation
OT  - intestinal ischemia/reperfusion
OT  - neutrophil extracellular traps
COIS- The author(s) declared no potential conflicts of interest with respect to the 
      research, authorship and/or publication of this article.
EDAT- 2023/09/12 12:42
MHDA- 2023/09/12 12:43
PMCR- 2023/09/12
CRDT- 2023/09/12 06:43
PHST- 2023/09/12 12:43 [medline]
PHST- 2023/09/12 12:42 [pubmed]
PHST- 2023/09/12 06:43 [entrez]
PHST- 2023/09/12 00:00 [pmc-release]
AID - 10.1177_03946320231193832 [pii]
AID - 10.1177/03946320231193832 [doi]
PST - ppublish
SO  - Int J Immunopathol Pharmacol. 2023 Jan-Dec;37:3946320231193832. doi: 
      10.1177/03946320231193832.