PMID- 36479683
OWN - NLM
STAT- MEDLINE
DCOM- 20230314
LR  - 20230415
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Linking)
VI  - 180
IP  - 8
DP  - 2023 Apr
TI  - Chemotherapy-induced phlebitis via the GBP5/NLRP3 inflammasome axis and the 
      therapeutic effect of aescin.
PG  - 1132-1147
LID - 10.1111/bph.16002 [doi]
AB  - BACKGROUND AND PURPOSE: Intravenous infusion of chemotherapy drugs can cause 
      severe chemotherapy-induced phlebitis (CIP) in patients. However, the underlying 
      mechanism of CIP development remains unclear. EXPERIMENTAL APPROACH: 
      RNA-sequencing analysis was used to identify potential disease targets in CIP. 
      Guanylate binding protein-5 (GBP5) genetic deletion approaches also were used to 
      investigate the role of GBP5 in NLR family pyrin domain containing 3 (NLRP3) 
      inflammasome activation in lipopolysaccharide (LPS) primed murine 
      bone-marrow-derived macrophages (BMDMs) induced by vinorelbine (VIN) in vitro and 
      in mouse models of VIN-induced CIP in vivo. The anti-CIP effect of aescin was 
      evaluated, both in vivo and in vivo. KEY RESULTS: Here, we show that the 
      expression of GBP5 was upregulated in human peripheral blood mononuclear cells 
      from CIP patients. Genetic ablation of GBP5 in murine macrophages significantly 
      alleviated VIN-induced CIP in the experimental mouse model. Mechanistically, GBP5 
      contributed to the inflammatory responses through activating NLRP3 inflammasome 
      and driving the production of the inflammatory cytokine IL-1beta. Moreover, aescin, 
      a mixture of triterpene saponins extracted from horse chestnut seed, can 
      alleviate CIP by inhibiting the GBP5/NLRP3 axis. CONCLUSION AND IMPLICATIONS: 
      These findings suggest that GBP5 is an important regulator of NLRP3 inflammasome 
      in CIP mouse model. Our work further reveals that aescin may serve as a promising 
      candidate in the clinical treatment of CIP.
CI  - (c) 2022 British Pharmacological Society.
FAU - Liu, Peng
AU  - Liu P
AD  - School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, China.
FAU - Ye, Lichun
AU  - Ye L
AD  - School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.
FAU - Ren, Yongshen
AU  - Ren Y
AD  - School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, China.
FAU - Zhao, Guodun
AU  - Zhao G
AD  - Center for Neurological and Psychiatric Research and Drug Discovery, Shanghai 
      Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
AD  - School of Chinese Materia Medica, Nanjing University of Chinese Medicine, 
      Nanjing, China.
FAU - Zhang, Yun
AU  - Zhang Y
AD  - Center for Neurological and Psychiatric Research and Drug Discovery, Shanghai 
      Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
AD  - School of Chinese Materia Medica, Nanjing University of Chinese Medicine, 
      Nanjing, China.
FAU - Lu, Shaojuan
AU  - Lu S
AD  - School of Medicine, Tongji University, Shanghai, China.
FAU - Li, Qiang
AU  - Li Q
AD  - School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, China.
FAU - Wu, Chen
AU  - Wu C
AD  - School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, China.
FAU - Bai, Lijie
AU  - Bai L
AD  - School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, China.
FAU - Zhang, Zhongyun
AU  - Zhang Z
AD  - School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, China.
FAU - Zhao, Zhongqiu
AU  - Zhao Z
AD  - Center for the Study of Itch, Department of Anesthesiology, Washington University 
      School of Medicine in St. Louis, St. Louis, Missouri, USA.
AD  - Barnes-Jewish Hospital, St. Louis, Missouri, USA.
FAU - Shi, Zhaohua
AU  - Shi Z
AD  - School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.
FAU - Yin, Shijin
AU  - Yin S
AD  - School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, China.
FAU - Liao, Maochuan
AU  - Liao M
AD  - School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, China.
FAU - Lan, Zhou
AU  - Lan Z
AD  - School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.
FAU - Feng, Jing
AU  - Feng J
AUID- ORCID: 0000-0001-6726-7912
AD  - Center for Neurological and Psychiatric Research and Drug Discovery, Shanghai 
      Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
AD  - School of Chinese Materia Medica, Nanjing University of Chinese Medicine, 
      Nanjing, China.
FAU - Chen, Lvyi
AU  - Chen L
AUID- ORCID: 0000-0002-4318-3033
AD  - School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221226
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 6805-41-0 (Escin)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Interleukin-1beta)
RN  - 0 (GBP5 protein, human)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 3.6.1.- (Gbp5 protein, mouse)
RN  - 0 (Nlrp3 protein, mouse)
SB  - IM
MH  - Humans
MH  - Animals
MH  - Mice
MH  - Inflammasomes/metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - Escin
MH  - Leukocytes, Mononuclear/metabolism
MH  - *Phlebitis
MH  - *Antineoplastic Agents
MH  - Lipopolysaccharides/pharmacology
MH  - Interleukin-1beta/metabolism
MH  - GTP-Binding Proteins/metabolism
OTO - NOTNLM
OT  - GBP5
OT  - NLRP3 inflammasome
OT  - aescin
OT  - phlebitis
OT  - vinorelbine
EDAT- 2022/12/09 06:00
MHDA- 2023/03/15 06:00
CRDT- 2022/12/08 14:15
PHST- 2022/10/03 00:00 [revised]
PHST- 2022/04/24 00:00 [received]
PHST- 2022/11/28 00:00 [accepted]
PHST- 2022/12/09 06:00 [pubmed]
PHST- 2023/03/15 06:00 [medline]
PHST- 2022/12/08 14:15 [entrez]
AID - 10.1111/bph.16002 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2023 Apr;180(8):1132-1147. doi: 10.1111/bph.16002. Epub 2022 Dec 
      26.