PMID- 37582314
OWN - NLM
STAT- MEDLINE
DCOM- 20230923
LR  - 20230923
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 123
DP  - 2023 Oct
TI  - Cannabinoid receptor 2 alleviates sepsis-associated acute lung injury by 
      modulating maturation of dendritic cells.
PG  - 110771
LID - S1567-5769(23)01096-2 [pii]
LID - 10.1016/j.intimp.2023.110771 [doi]
AB  - BACKGROUND: Dendritic cells (DCs) play a key role in a variety of inflammatory 
      lung diseases, but their role in sepsis-associated acute lung injury (SA-ALI) is 
      currently not been illuminated. Cannabinoid receptor 2 (CNR2) has been reported 
      to regulate the DCs maturation. However, whether the CNR2 in DCs contributes to 
      therapeutic therapy for SA-ALI remain unclear. In current study, the role of CNR2 
      on DCs maturation and inflammatory during SA-ALI is to explored. METHODS: First, 
      the CNR2 level was analyzed in isolated Peripheral Blood Mononuclear Cells 
      (PBMCs) and Bronchoalveolar Lavage Fluid (BALF) from patient with SA-ALI by 
      qRT-PCR and flow cytometry. Subsequently, HU308, a specific agonist of CNR2, and 
      SR144528, a specific antagonist of CNR2, were introduced to explore the function 
      of CNR2 on DCs maturation and inflammatory during SA-ALI. Finally, CNR2 
      conditional knockout mice were generated to further confirm the function of DCs 
      maturation and Inflammation during SA-ALI. RESULTS: First, we found that the 
      expression of CNR2 on DCs was decreased in patient with SA-ALI. Besides, the 
      result showed HU308 could decrease the maturation of DCs and the level of 
      inflammatory cytokines, simultaneously reduce pulmonary pathological injury after 
      LPS-induced sepsis in mice. In contrast of HU308, SR144528 exhibits opposite 
      function of DCs maturate, inflammatory cytokines and lung pathological injury. 
      Furthermore, comparing with SR144528 treatment, similar results were obtained in 
      DCs specific CNR2 knockout mice after LPS treatment. CONCLUSION: CNR2 could 
      alleviate SA-ALI by modulating maturation of DCs and inflammatory factors levels. 
      Targeting CNR2 signaling specifically in DCs has therapeutic potential for the 
      treatment of SA-ALI.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Zhao, Feng-Zhi
AU  - Zhao FZ
AD  - Department of Intensive Care Unit, the First Affiliated Hospital of Jinan 
      University, Guangzhou, Guangdong, China.
FAU - Gu, Wan-Jie
AU  - Gu WJ
AD  - Department of Intensive Care Unit, the First Affiliated Hospital of Jinan 
      University, Guangzhou, Guangdong, China.
FAU - Li, Long-Zhu
AU  - Li LZ
AD  - Department of Intensive Care Unit, the First Affiliated Hospital of Jinan 
      University, Guangzhou, Guangdong, China.
FAU - Qu, Zhong-Kai
AU  - Qu ZK
AD  - Department of Intensive Care Unit, the First Affiliated Hospital of Jinan 
      University, Guangzhou, Guangdong, China.
FAU - Xu, Meng-Yuan
AU  - Xu MY
AD  - Department of Intensive Care Unit, the First Affiliated Hospital of Jinan 
      University, Guangzhou, Guangdong, China.
FAU - Liu, Kai
AU  - Liu K
AD  - Department of Intensive Care Unit, the First Affiliated Hospital of Jinan 
      University, Guangzhou, Guangdong, China.
FAU - Zhang, Feng
AU  - Zhang F
AD  - Department of Intensive Care Unit, the First Affiliated Hospital of Jinan 
      University, Guangzhou, Guangdong, China.
FAU - Liu, Hui
AU  - Liu H
AD  - Department of Intensive Care Unit, the First Affiliated Hospital of Jinan 
      University, Guangzhou, Guangdong, China.
FAU - Xu, Jun
AU  - Xu J
AD  - Department of Intensive Care Unit, the First Affiliated Hospital of Jinan 
      University, Guangzhou, Guangdong, China. Electronic address: junxujnu@163.com.
FAU - Yin, Hai-Yan
AU  - Yin HY
AD  - Department of Intensive Care Unit, the First Affiliated Hospital of Jinan 
      University, Guangzhou, Guangdong, China. Electronic address: 
      yinhaiyan167@163.com.
LA  - eng
PT  - Journal Article
DEP - 20230813
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Cytokines)
RN  - 8I5L034D55 (HU 308)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Receptors, Cannabinoid)
RN  - 0 (SR 144528)
RN  - 0 (CNR2 protein, human)
RN  - 0 (Cnr2 protein, mouse)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - *Acute Lung Injury/chemically induced
MH  - Cytokines/metabolism
MH  - Dendritic Cells/metabolism
MH  - Leukocytes, Mononuclear/metabolism
MH  - Lipopolysaccharides
MH  - Lung/pathology
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Receptors, Cannabinoid
MH  - *Sepsis/metabolism
OTO - NOTNLM
OT  - Cannabinoid receptor 2
OT  - Dendritic cells
OT  - HU308
OT  - SR144528
OT  - Sepsis-associated acute lung injury
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- 2023/08/15 18:41
MHDA- 2023/09/22 06:42
CRDT- 2023/08/15 18:00
PHST- 2023/05/18 00:00 [received]
PHST- 2023/08/03 00:00 [revised]
PHST- 2023/08/03 00:00 [accepted]
PHST- 2023/09/22 06:42 [medline]
PHST- 2023/08/15 18:41 [pubmed]
PHST- 2023/08/15 18:00 [entrez]
AID - S1567-5769(23)01096-2 [pii]
AID - 10.1016/j.intimp.2023.110771 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2023 Oct;123:110771. doi: 10.1016/j.intimp.2023.110771. Epub 
      2023 Aug 13.