PMID- 37801969
OWN - NLM
STAT- MEDLINE
DCOM- 20231113
LR  - 20231113
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 124
IP  - Pt B
DP  - 2023 Nov
TI  - Orexin A alleviates LPS-induced acute lung injury by inhibiting macrophage 
      activation through JNK-mediated autophagy.
PG  - 111018
LID - S1567-5769(23)01343-7 [pii]
LID - 10.1016/j.intimp.2023.111018 [doi]
AB  - Crosstalk between the central nervous system and immune system by the 
      neuroendocrine and autonomic nervous systems is critical during the inflammatory 
      response. Exposure to endotoxin alters the activity of hypothalamic homeostatic 
      systems, resulting in changed transmitter release within the brain. This study 
      investigated the effects and cellular molecular mechanisms of neurogenic and 
      exogenous orexin-A (OXA) in LPS-induced acute lung injury (ALI). We found the 
      production of OXA in the hypothalamus and lungs was both decreased following LPS 
      infection. LPS-induced lung injury including the destruction of the structure, 
      inflammatory cell infiltration, and pro-inflammatory cytokines generation was 
      aggravated in mice in which orexin neurons were lesioned with the neurotoxin 
      orexin-saporin (orexin-SAP). Administration of exogenous OXA greatly improved 
      lung pathology and reduced inflammatory response. Orexin receptors were found in 
      cultured mouse bone marrow-derived macrophages (BMDMs) and lung macrophages 
      (LMs), adoptive transfer of OXA-treated macrophages showed alleviative lung 
      injury compared to adoptive transfer of macrophages without OXA treatment. 
      Mechanistically, it is the induction of autophagy via JNK activation that is 
      responsible for OXA to suppress macrophage-derived pro-inflammatory cytokine 
      production. These findings highlight the importance of neuro-immune crosstalk and 
      indicate that OXA may be a potential therapeutic agent in the treatment of ALI.
CI  - Copyright (c) 2023. Published by Elsevier B.V.
FAU - Nie, Yunjuan
AU  - Nie Y
AD  - Affiliated Hospital of Jiangnan University, 1000 Hefeng Road, Wuxi 214000, 
      Jiangsu Province, PR China; Department of Basic Medicine, Wuxi School of 
      Medicine, Jiangnan University, Wuxi, Jiangsu 214122, PR China.
FAU - Liang, Junjie
AU  - Liang J
AD  - Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 
      Jiangsu 214122, PR China.
FAU - Sun, Jie
AU  - Sun J
AD  - Department of Pharmacy, Wuxi Higher Health Vocational Technology School, Wuxi 
      214000, PR China.
FAU - Li, Jiao
AU  - Li J
AD  - Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 
      Jiangsu 214122, PR China.
FAU - Zhai, Xiaorun
AU  - Zhai X
AD  - Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 
      Jiangsu 214122, PR China.
FAU - Zhao, Peng
AU  - Zhao P
AD  - Affiliated Hospital of Jiangnan University, 1000 Hefeng Road, Wuxi 214000, 
      Jiangsu Province, PR China; Department of Basic Medicine, Wuxi School of 
      Medicine, Jiangnan University, Wuxi, Jiangsu 214122, PR China. Electronic 
      address: zhaopeng336@jiangnan.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20231004
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Orexins)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Acute Lung Injury/chemically induced/drug therapy/pathology
MH  - Autophagy
MH  - Cytokines
MH  - *Lipopolysaccharides
MH  - Lung/pathology
MH  - Macrophage Activation
MH  - Mice, Inbred C57BL
MH  - Orexins/therapeutic use/pharmacology
OTO - NOTNLM
OT  - Acute lung injury
OT  - Autophagy
OT  - JNK
OT  - Macrophage
OT  - Orexin A
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/10/07 00:41
MHDA- 2023/11/02 12:46
CRDT- 2023/10/06 18:10
PHST- 2023/07/07 00:00 [received]
PHST- 2023/09/16 00:00 [revised]
PHST- 2023/09/28 00:00 [accepted]
PHST- 2023/11/02 12:46 [medline]
PHST- 2023/10/07 00:41 [pubmed]
PHST- 2023/10/06 18:10 [entrez]
AID - S1567-5769(23)01343-7 [pii]
AID - 10.1016/j.intimp.2023.111018 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2023 Nov;124(Pt B):111018. doi: 
      10.1016/j.intimp.2023.111018. Epub 2023 Oct 4.