PMID- 34305926
OWN - NLM
STAT- MEDLINE
DCOM- 20211213
LR  - 20240226
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - Butorphanol Promotes Macrophage Phenotypic Transition to Inhibit Inflammatory 
      Lung Injury via kappa Receptors.
PG  - 692286
LID - 10.3389/fimmu.2021.692286 [doi]
LID - 692286
AB  - Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is 
      characterized by diffuse inflammation of the lung parenchyma and refractory 
      hypoxemia. Butorphanol is commonly used clinically for perioperative pain relief, 
      but whether butorphanol can regulate LPS-induced alveolar macrophage polarization 
      is unclear. In this study, we observed that butorphanol markedly attenuated 
      sepsis-induced lung tissue injury and mortality in mice. Moreover, butorphanol 
      also decreased the expression of M1 phenotype markers (TNF-alpha, IL-6, IL-1beta and 
      iNOS) and enhanced the expression of M2 marker (CD206) in alveolar macrophages in 
      the bronchoalveolar lavage fluid (BALF) of LPS-stimulated mice. Butorphanol 
      administration reduced LPS-induced numbers of proinflammatory (M1) macrophages 
      and increased numbers of anti-inflammatory (M2) macrophages in the lungs of mice. 
      Furthermore, we found that butorphanol-mediated suppression of the LPS-induced 
      increases in M1 phenotype marker expression (TNF-alpha, IL-6, IL-1beta and iNOS) in bone 
      marrow-derived macrophages (BMDMs), and this effect was reversed by kappa-opioid 
      receptor (KOR) antagonists. Moreover, butorphanol inhibited the interaction of 
      TLR4 with MyD88 and further suppressed NF-kappaB and MAPKs activation. In addition, 
      butorphanol prevented the Toll/IL-1 receptor domain-containing adaptor inducing 
      IFN-beta (TRIF)-mediated IFN signaling pathway. These effects were ameliorated by 
      KOR antagonists. Thus, butorphanol may promote macrophage polarization from a 
      proinflammatory to an anti-inflammatory phenotype secondary to the inhibition of 
      NF-kappaB, MAPKs, and the TRIF-mediated IFN signaling pathway through kappa receptors.
CI  - Copyright (c) 2021 Luan, Pan, Bu, Wu, Wang and Xu.
FAU - Luan, Guangxin
AU  - Luan G
AD  - Department of Anesthesiology, Affiliated Shanghai Sixth People's Hospital, 
      Shanghai Jiao Tong University, Shanghai, China.
FAU - Pan, Fan
AU  - Pan F
AD  - Department of Anesthesiology, Affiliated Shanghai Sixth People's Hospital, 
      Shanghai Jiao Tong University, Shanghai, China.
FAU - Bu, Lina
AU  - Bu L
AD  - Department of Anesthesiology, Affiliated Shanghai Sixth People's Hospital, 
      Shanghai Jiao Tong University, Shanghai, China.
FAU - Wu, Kaixuan
AU  - Wu K
AD  - Department of Anesthesiology, Affiliated Shanghai Sixth People's Hospital, 
      Shanghai Jiao Tong University, Shanghai, China.
FAU - Wang, Aizhong
AU  - Wang A
AD  - Department of Anesthesiology, Affiliated Shanghai Sixth People's Hospital, 
      Shanghai Jiao Tong University, Shanghai, China.
FAU - Xu, Xiaotao
AU  - Xu X
AD  - Department of Anesthesiology, Affiliated Shanghai Sixth People's Hospital, 
      Shanghai Jiao Tong University, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210707
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Opioid, kappa)
RN  - 0 (TICAM-1 protein, mouse)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - QV897JC36D (Butorphanol)
SB  - IM
MH  - Acute Lung Injury/immunology/metabolism/*prevention & control
MH  - Adaptor Proteins, Vesicular Transport/metabolism
MH  - Analgesics, Opioid/*pharmacology
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Butorphanol/*pharmacology
MH  - Cells, Cultured
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Lung/*drug effects/immunology/metabolism
MH  - Macrophages/*drug effects/immunology/metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NF-kappa B/metabolism
MH  - Phenotype
MH  - Pneumonia/immunology/metabolism/*prevention & control
MH  - Receptors, Opioid, kappa/*antagonists & inhibitors/metabolism
MH  - Signal Transduction
MH  - Mice
PMC - PMC8294090
OTO - NOTNLM
OT  - acute lung injury
OT  - butorphanol
OT  - inflammation
OT  - macrophage
OT  - kappa receptor
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/07/27 06:00
MHDA- 2021/12/15 06:00
PMCR- 2021/01/01
CRDT- 2021/07/26 06:24
PHST- 2021/04/08 00:00 [received]
PHST- 2021/06/21 00:00 [accepted]
PHST- 2021/07/26 06:24 [entrez]
PHST- 2021/07/27 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.692286 [doi]
PST - epublish
SO  - Front Immunol. 2021 Jul 7;12:692286. doi: 10.3389/fimmu.2021.692286. eCollection 
      2021.