PMID- 36706590
OWN - NLM
STAT- MEDLINE
DCOM- 20230308
LR  - 20230308
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 116
DP  - 2023 Mar
TI  - Putrescine accelerates the differentiation of bone marrow derived dendritic cells 
      via inhibiting phosphorylation of STAT3 at Tyr705.
PG  - 109739
LID - S1567-5769(23)00062-0 [pii]
LID - 10.1016/j.intimp.2023.109739 [doi]
AB  - Dendritic cells (DCs) play pivotal roles in immune responses. The differentiation 
      and function of DCs are regulated by environmental metabolites. Putrescine is 
      ubiquitous in various metabolic microenvironments and its immunoregulation has 
      been of increasing interest. However, the mechanisms associated with its 
      DC-induced immunoregulation remain unclear. In this study, we found putrescine 
      promoted induction of immature bone marrow derived DCs (BMDCs), along with the 
      increased phagocytosis and migration, and altered cytokine secretion in immature 
      BMDCs. Transcriptomic profiles indicated significantly impaired 
      inflammatory-related pathways, elevated oxidative phosphorylation, and decreased 
      p-STAT3 (Tyr705) expression. Additionally, putrescine performed minor influence 
      on the lipopolysaccharide (LPS)-induced maturation of BMDCs but significantly 
      impaired LPS-induced DC-elicited allogeneic T-cell proliferation as well as the 
      cytokine secretion. Furthermore, molecular docking and dynamics on the 
      conjugation between putrescine and STAT3 revealed that putrescine could be stably 
      bound to the hydrophilic cavity in STAT3 and performed significant influence on 
      the Tyr705 phosphorylation. CUT&Tag analysis uncovered altered motifs, 
      downregulated IFN-gamma response, and upregulated p53 pathway in Putrescine group 
      compared with Control group. In summary, our results demonstrated for the first 
      time that putrescine might accelerate the differentiation of BMDCs by inhibiting 
      the phosphorylation of STAT3 at Tyr705. Given that both DCs and putrescine have 
      ubiquitous and distinct roles in various immune responses and pathogeneses, our 
      findings may provide more insights into polyamine immunoregulation on DCs, as 
      well as distinct strategies in the clinical utilization of DCs by targeting 
      polyamines.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Huang, Panpan
AU  - Huang P
AD  - Department of Immunology, Binzhou Medical University, Yantai, China.
FAU - Wang, Mengyang
AU  - Wang M
AD  - Department of Immunology, Binzhou Medical University, Yantai, China.
FAU - Lu, Zixuan
AU  - Lu Z
AD  - Department of Immunology, Binzhou Medical University, Yantai, China.
FAU - Shi, Shaojie
AU  - Shi S
AD  - Department of Immunology, Binzhou Medical University, Yantai, China.
FAU - Wei, Xia
AU  - Wei X
AD  - Department of Immunology, Binzhou Medical University, Yantai, China.
FAU - Bi, Chenxiao
AU  - Bi C
AD  - Department of Immunology, Binzhou Medical University, Yantai, China.
FAU - Wang, Guoyan
AU  - Wang G
AD  - Medical Laboratory Science, Yantai Affiliated Hospital of ao'deBinzhou Medical 
      University, Yantai, China.
FAU - Liu, Hong
AU  - Liu H
AD  - The 2nd Medical College of Binzhou Medical University, Binzhou Medical 
      University, Yantai, China.
FAU - Hu, Tao
AU  - Hu T
AD  - Department of Immunology, Binzhou Medical University, Yantai, China. Electronic 
      address: taohu@bzmc.edu.cn.
FAU - Wang, Bin
AU  - Wang B
AD  - Department of Immunology, Binzhou Medical University, Yantai, China. Electronic 
      address: bwang_bzmc@bzmc.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230126
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - V10TVZ52E4 (Putrescine)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Cytokines)
SB  - IM
MH  - Phosphorylation
MH  - *Putrescine/pharmacology/metabolism
MH  - *Lipopolysaccharides/metabolism
MH  - Bone Marrow
MH  - Molecular Docking Simulation
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Cytokines/metabolism
MH  - Dendritic Cells
MH  - Bone Marrow Cells/metabolism
OTO - NOTNLM
OT  - DC
OT  - Mitochondrial respiratory activity
OT  - Putrescine
OT  - STAT3
OT  - Th2 response
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- 2023/01/28 06:00
MHDA- 2023/03/09 06:00
CRDT- 2023/01/27 18:12
PHST- 2022/11/11 00:00 [received]
PHST- 2023/01/12 00:00 [revised]
PHST- 2023/01/12 00:00 [accepted]
PHST- 2023/01/28 06:00 [pubmed]
PHST- 2023/03/09 06:00 [medline]
PHST- 2023/01/27 18:12 [entrez]
AID - S1567-5769(23)00062-0 [pii]
AID - 10.1016/j.intimp.2023.109739 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2023 Mar;116:109739. doi: 10.1016/j.intimp.2023.109739. Epub 
      2023 Jan 26.