PMID- 37606515
OWN - NLM
STAT- MEDLINE
DCOM- 20240116
LR  - 20240116
IS  - 1532-2513 (Electronic)
IS  - 0892-3973 (Linking)
VI  - 45
IP  - 6
DP  - 2023 Dec
TI  - Ciclopirox mitigates inflammatory response in LPS-induced septic shock via 
      inactivation of SORT1-mediated wnt/beta-Catenin signaling pathway.
PG  - 701-708
LID - 10.1080/08923973.2023.2231628 [doi]
AB  - OBJECTIVE: Septic shock, the most severe stage of sepsis, is a deadly 
      inflammatory disorder with high mortality. Ciclopirox (CPX) is a broad-spectrum 
      antimycotic agent which also exerts anti-inflammatory effects in human diseases. 
      However, whether CPX can relieve inflammatory response in LPS-induced septic 
      shock remains unclear. MATERIALS AND METHODS: Male C57BL/6 mice LPS were injected 
      intraperitoneally with LPS to simulate septic shock in vivo. RAW264.7 cells and 
      bone marrow-derived macrophages (BMDMs) were subject to LPS treatment to simulate 
      septic shock in vitro. ELISA was applied to detect the level of pro-inflammatory 
      cytokines. Cell viability was assessed by CCK-8 assay. Protein levels was 
      detected by western blotting. RESULTS: CPX enhanced the survival rate and 
      attenuated inflammation in mice with LPS-induced septic shock. Similarly, CPX 
      dose-dependently mitigated LPS-induced inflammation in BMDMs. It was also found 
      that Sortilin 1 (SORT1) was upregulated in both in vivo and in vitro models of 
      LPS-induced septic shock. In addition, SORT1 overexpression counteracted the 
      alleviative effects of CPX on the inflammation response of LPS-challenged BMDMs 
      by activating the Wnt/beta-Catenin signaling. Furthermore, BML-284 (a Wnt/beta-Catenin 
      agonist) treatment also abrogated CPX-mediated moderation of LPS-triggered 
      inflammatory reaction in BMDMs. CONCLUSIONS: In sum, we found that CPX protected 
      against LPS-induced septic shock by mitigating inflammation via SORT1-mediated 
      Wnt/beta-Catenin signaling pathway.
FAU - Zhou, Liangliang
AU  - Zhou L
AD  - Department of Emergency Intensive Care Medicine and Department of Emergency 
      Medicine, The Fourth Affiliated Hospital of Nantong University/The First People's 
      Hospital of Yancheng, Yancheng, Jiangsu, China.
FAU - He, Yingfeng
AU  - He Y
AD  - Department of Emergency Intensive Care Medicine, The Fourth Affiliated Hospital 
      of Nantong University/The First People's Hospital of Yancheng, Yancheng, Jiangsu, 
      China.
FAU - Deng, Yijun
AU  - Deng Y
AD  - Department of Emergency Intensive Care Medicine, The Fourth Affiliated Hospital 
      of Nantong University/The First People's Hospital of Yancheng, Yancheng, Jiangsu, 
      China.
FAU - Li, Xinxin
AU  - Li X
AD  - Department of Emergency Intensive Care Medicine, The Fourth Affiliated Hospital 
      of Nantong University/The First People's Hospital of Yancheng, Yancheng, Jiangsu, 
      China.
FAU - Wang, Wei
AU  - Wang W
AD  - Department of Emergency Intensive Care Medicine, The Fourth Affiliated Hospital 
      of Nantong University/The First People's Hospital of Yancheng, Yancheng, Jiangsu, 
      China.
FAU - Chen, Jianjun
AU  - Chen J
AD  - Department of Emergency Intensive Care Medicine and Department of Emergency 
      Medicine, The Fourth Affiliated Hospital of Nantong University/The First People's 
      Hospital of Yancheng, Yancheng, Jiangsu, China.
LA  - eng
PT  - Journal Article
DEP - 20230822
PL  - England
TA  - Immunopharmacol Immunotoxicol
JT  - Immunopharmacology and immunotoxicology
JID - 8800150
RN  - 19W019ZDRJ (Ciclopirox)
RN  - 0 (Lipopolysaccharides)
RN  - Z020Y8WIJ4 (sortilin)
RN  - 0 (Adaptor Proteins, Vesicular Transport)
SB  - IM
MH  - *Ciclopirox/pharmacology
MH  - *Shock, Septic/chemically induced/drug therapy
MH  - Lipopolysaccharides
MH  - Male
MH  - Animals
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - RAW 264.7 Cells
MH  - Macrophages/drug effects
MH  - *Adaptor Proteins, Vesicular Transport/genetics
MH  - *Wnt Signaling Pathway
MH  - *Inflammation/drug therapy
OTO - NOTNLM
OT  - Ciclopirox
OT  - LPS
OT  - SORT1
OT  - Wnt/beta-Catenin
OT  - septic shock
EDAT- 2023/08/22 13:42
MHDA- 2023/12/06 06:41
CRDT- 2023/08/22 09:24
PHST- 2023/12/06 06:41 [medline]
PHST- 2023/08/22 13:42 [pubmed]
PHST- 2023/08/22 09:24 [entrez]
AID - 10.1080/08923973.2023.2231628 [doi]
PST - ppublish
SO  - Immunopharmacol Immunotoxicol. 2023 Dec;45(6):701-708. doi: 
      10.1080/08923973.2023.2231628. Epub 2023 Aug 22.