PMID- 33638265
OWN - NLM
STAT- MEDLINE
DCOM- 20211119
LR  - 20211119
IS  - 1747-0285 (Electronic)
IS  - 1747-0277 (Linking)
VI  - 97
IP  - 6
DP  - 2021 Jun
TI  - Toll-like receptor 4 antagonist FP7 alleviates lipopolysaccharide-induced septic 
      shock via NF-kB signaling pathway.
PG  - 1151-1157
LID - 10.1111/cbdd.13837 [doi]
AB  - Septic shock is the most severe complication of sepsis occurs when body has an 
      overwhelming response to infection, making it the most prevalent cause of deaths 
      in surgical intensive-care units. Therefore, it is urgent to understand its 
      pathogenesis and develop new therapeutic candidate drugs for septic shock. Here, 
      we explored the effect of FP7, an antagonist of Toll-like receptor 4 (TLR4), in 
      the septic shock. First, we injected mice with FP7 and found that FP7 had no 
      effect on immune cells. Then, bone marrow-derived macrophages (BMDMs) isolated 
      from mice were pretreated with FP7 followed by lipopolysaccharide (LPS) 
      stimulation, and FP7 specifically suppressed LPS-induced inflammatory responses 
      in BMDMs via Nuclear factor kappa-light-chain enhancer of activated B cells 
      (NF-kappaB) signaling pathway, with no effect on other TLRs-mediated inflammations. 
      Finally, we injected mice with LPS and D-galactosamine to induce septic shock, 
      followed by the treatment of FP7, and FP7 significantly increased survival rate, 
      improved lung necrosis, and inhibited the secretions of proinflammatory cytokines 
      in the mice with septic shock. Therefore, our study suggested that FP7 had a 
      protective role in septic shock and it might serve as a promising therapeutic 
      candidate drug to treat septic shock.
CI  - (c) 2021 John Wiley & Sons Ltd.
FAU - Li, Chao
AU  - Li C
AD  - Department of Emergency, Xingtai People's Hospital of Hebei Province, Xingtai, 
      China.
FAU - Wang, Junhui
AU  - Wang J
AD  - Department of Emergency, Xingtai People's Hospital of Hebei Province, Xingtai, 
      China.
FAU - Zhao, Mailiang
AU  - Zhao M
AD  - Department of Emergency, Xingtai People's Hospital of Hebei Province, Xingtai, 
      China.
FAU - Zhang, Sheng
AU  - Zhang S
AD  - Department of Emergency, Xingtai People's Hospital of Hebei Province, Xingtai, 
      China.
FAU - Zhang, Yanwei
AU  - Zhang Y
AD  - Department of Emergency, Xingtai People's Hospital of Hebei Province, Xingtai, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20210306
PL  - England
TA  - Chem Biol Drug Des
JT  - Chemical biology & drug design
JID - 101262549
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Protective Agents)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Animals
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Lipopolysaccharides/toxicity
MH  - Macrophages/cytology/drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/*metabolism
MH  - Protective Agents/chemistry/*pharmacology/therapeutic use
MH  - Shock, Septic/drug therapy/etiology/mortality
MH  - Signal Transduction/*drug effects
MH  - Survival Rate
MH  - Toll-Like Receptor 4/*antagonists & inhibitors/metabolism
OTO - NOTNLM
OT  - FP7
OT  - Mice
OT  - TLR4
OT  - inflammation
OT  - septic shock
EDAT- 2021/02/28 06:00
MHDA- 2021/11/20 06:00
CRDT- 2021/02/27 05:44
PHST- 2021/01/23 00:00 [revised]
PHST- 2020/11/17 00:00 [received]
PHST- 2021/02/21 00:00 [accepted]
PHST- 2021/02/28 06:00 [pubmed]
PHST- 2021/11/20 06:00 [medline]
PHST- 2021/02/27 05:44 [entrez]
AID - 10.1111/cbdd.13837 [doi]
PST - ppublish
SO  - Chem Biol Drug Des. 2021 Jun;97(6):1151-1157. doi: 10.1111/cbdd.13837. Epub 2021 
      Mar 6.