PMID- 32274095
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220817
IS  - 2072-1439 (Print)
IS  - 2077-6624 (Electronic)
IS  - 2072-1439 (Linking)
VI  - 12
IP  - 3
DP  - 2020 Mar
TI  - Inhibition of the endoplasmic reticulum (ER) stress-associated IRE-1/XBP-1 
      pathway alleviates acute lung injury via modulation of macrophage activation.
PG  - 284-295
LID - 10.21037/jtd.2020.01.45 [doi]
AB  - BACKGROUND: Both endoplasmic reticulum (ER) stress and macrophage diversity 
      contribute to inflammatory processes in lung injury. However, the interaction 
      between ER stress and macrophage M1/M2 imbalance in lung inflammation remains 
      unclear. The present study, thus, aimed to evaluate the role of ER 
      stress-mediated macrophage phenotype changes in lipopolysaccharide (LPS)-induced 
      acute lung injury (ALI). METHODS: Lung inflammation and injury were examined in a 
      murine model of LPS-induced ALI with or without ER stress inhibitors. Alveolar 
      macrophage (AM) polarization was determined by flow cytometry. Bone 
      marrow-derived macrophages (BMDMs) were treated with either an ER stress inducer, 
      inhibitor, or an IRE-1 endonuclease inhibitor before being polarized to an M1 and 
      M2 phenotype. The macrophage polarization status was examined via RT-PCR and flow 
      cytometry. RESULTS: Our results indicated that ER stress and IRE-1/XBP-1 
      signaling are activated in LPS-induced ALI. Furthermore, we observed that AM 
      polarizes to an inflammatory phenotype upon exposure to LPS in the induction 
      phase and an anti-inflammatory phenotype in the resolution phase of lung 
      inflammation. Inhibition of ER stress attenuated the pathophysiological features 
      of LPS-induced lung inflammation/injury, as evidenced by a decrease in 
      bronchoalveolar lavage (BAL) protein levels, the number of inflammatory cells, 
      and the expression level of inflammatory mediators. In addition, the ER stress 
      inducer promoted M1 polarization and the switch from M2 to M1 in BMDMs, whereas 
      inhibition of ER stress and XBP-1 splicing suppressed M1 but did not promote M2, 
      both in vivo and in vitro. CONCLUSIONS: Our results demonstrated that inhibition 
      of the ER stress-associated IRE-1/XBP-1 signaling pathway suppresses M1 
      polarization and ameliorates LPS-induced lung injury. This indicates that the 
      interaction between ER stress and macrophage polarization might be a novel 
      therapeutic target for endotoxin-induced lung inflammatory disorders.
CI  - 2020 Journal of Thoracic Disease. All rights reserved.
FAU - Zhao, Yanfeng
AU  - Zhao Y
AD  - Department of Thoracic Surgery, Shanghai Pulmonary Hospital affiliated to Tongji 
      University, Shanghai 200433, China.
FAU - Jiang, Yan
AU  - Jiang Y
AD  - Department of Thoracic Surgery, Shanghai Pulmonary Hospital affiliated to Tongji 
      University, Shanghai 200433, China.
FAU - Chen, Linsong
AU  - Chen L
AD  - Department of Thoracic Surgery, Shanghai Pulmonary Hospital affiliated to Tongji 
      University, Shanghai 200433, China.
FAU - Zheng, Xinlin
AU  - Zheng X
AD  - Department of Thoracic Surgery, Weifang Hospital of Traditional Chinese Medicine, 
      Weifang 261041, China.
FAU - Zhu, Junjie
AU  - Zhu J
AD  - Department of Thoracic Surgery, Shanghai Pulmonary Hospital affiliated to Tongji 
      University, Shanghai 200433, China.
FAU - Song, Xiao
AU  - Song X
AD  - Department of Thoracic Surgery, Shanghai Pulmonary Hospital affiliated to Tongji 
      University, Shanghai 200433, China.
FAU - Shi, Jinghan
AU  - Shi J
AD  - Department of Thoracic Surgery, Shanghai Pulmonary Hospital affiliated to Tongji 
      University, Shanghai 200433, China.
FAU - Li, Yuping
AU  - Li Y
AD  - Department of Thoracic Surgery, Shanghai Pulmonary Hospital affiliated to Tongji 
      University, Shanghai 200433, China.
FAU - He, Wenxin
AU  - He W
AD  - Department of Thoracic Surgery, Shanghai Pulmonary Hospital affiliated to Tongji 
      University, Shanghai 200433, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - J Thorac Dis
JT  - Journal of thoracic disease
JID - 101533916
PMC - PMC7139036
OTO - NOTNLM
OT  - Acute lung injury (ALI)
OT  - endoplasmic reticulum stress (ER stress)
OT  - inflammation
OT  - lipopolysaccharide (LPS)
OT  - macrophage polarization
COIS- Conflicts of Interest: The authors have no conflicts of interest to declare.
EDAT- 2020/04/11 06:00
MHDA- 2020/04/11 06:01
PMCR- 2020/03/01
CRDT- 2020/04/11 06:00
PHST- 2020/04/11 06:00 [entrez]
PHST- 2020/04/11 06:00 [pubmed]
PHST- 2020/04/11 06:01 [medline]
PHST- 2020/03/01 00:00 [pmc-release]
AID - jtd-12-03-284 [pii]
AID - 10.21037/jtd.2020.01.45 [doi]
PST - ppublish
SO  - J Thorac Dis. 2020 Mar;12(3):284-295. doi: 10.21037/jtd.2020.01.45.