PMID- 31524226
OWN - NLM
STAT- MEDLINE
DCOM- 20200204
LR  - 20200204
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Linking)
VI  - 44
IP  - 3
DP  - 2019 Sep
TI  - Biologically active 1,25-dihydroxyvitamin D3 protects against experimental sepsis 
      by negatively regulating the Toll-like receptor 4/myeloid differentiation primary 
      response gene 88/Toll-IL-1 resistance-domain-containing adapter-inducing 
      interferon-beta signaling pathway.
PG  - 1151-1160
LID - 10.3892/ijmm.2019.4266 [doi]
AB  - The hormonally active form of vitamin D (VD), 1,25‑dihydroxyvitamin D3, has been 
      reported to be a key immunoregulator in the reduction of inflammation. In this 
      study, we investigated the effects of VD in an experimental sepsis cell model, 
      and the underlying mechanisms. The sepsis cell model was first established in 
      monocytes, isolated from newborns and healthy adults, which were stimulation with 
      lipopolysaccharide (LPS). We observed that cell viability was significantly 
      impaired in the monocytes after LPS stimulation, using a Cell Counting Kit‑8 and 
      trypan blue assays. Additionally, ELISA revealed that LPS stimulation 
      significantly elevated the expression of interleukin 6 (IL‑6), IL‑10 and tumor 
      necrosis factor‑alpha (TNF‑alpha). The expression levels of Toll‑like receptor (TLR4), 
      myeloid differentiation primary response gene 88 (MyD88), and Toll‑IL‑1 
      resistance‑domain‑containing adapter‑inducing interferon‑beta (TRIF) mRNA were also 
      significantly elevated under LPS stimulation using reverse 
      transcription‑quantitative PCR and western blot analysis. VD treatment could 
      significantly suppress the effects of LPS simulation on monocytes by negatively 
      regulating inflammatory cytokines and TLR4/MyD88/TRIF signaling. Furthermore, a 
      regulatory feedback mechanism was proposed to involve TLR4, MyD88 and TRIF in the 
      sepsis cell model. In conclusion, VD may effectively decrease the release of 
      inflammatory cytokines by inhibiting the TLR4/MyD88/TRIF signaling pathway, could 
      be considered as a potential therapeutic agent for the treatment of sepsis.
FAU - Zheng, Ge
AU  - Zheng G
AD  - Department of Pediatrics, Ruian People's Hospital, Ruian, Zhejiang 325200, P.R. 
      China.
FAU - Wen, Na
AU  - Wen N
AD  - Department of Pediatrics, Ruian People's Hospital, Ruian, Zhejiang 325200, P.R. 
      China.
FAU - Pan, Minli
AU  - Pan M
AD  - Department of Pediatrics, Ruian People's Hospital, Ruian, Zhejiang 325200, P.R. 
      China.
FAU - Huang, Yumao
AU  - Huang Y
AD  - Department of Pediatrics, Ruian People's Hospital, Ruian, Zhejiang 325200, P.R. 
      China.
FAU - Li, Zhishu
AU  - Li Z
AD  - Department of Pediatrics, Ruian People's Hospital, Ruian, Zhejiang 325200, P.R. 
      China.
LA  - eng
PT  - Journal Article
DEP - 20190705
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Protective Agents)
RN  - 0 (TICAM1 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - FXC9231JVH (Calcitriol)
SB  - IM
MH  - Adaptor Proteins, Vesicular Transport/*metabolism
MH  - Adult
MH  - Animals
MH  - Calcitriol/*pharmacology
MH  - Case-Control Studies
MH  - Cytokines/metabolism
MH  - Female
MH  - Gene Expression Regulation
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - Male
MH  - Middle Aged
MH  - Monocytes/metabolism
MH  - Myeloid Differentiation Factor 88/*metabolism
MH  - Protective Agents/*pharmacology
MH  - Sepsis/*etiology/*metabolism
MH  - Signal Transduction
MH  - Toll-Like Receptor 4/genetics/*metabolism
EDAT- 2019/09/17 06:00
MHDA- 2020/02/06 06:00
CRDT- 2019/09/17 06:00
PHST- 2018/11/03 00:00 [received]
PHST- 2019/06/18 00:00 [accepted]
PHST- 2019/09/17 06:00 [pubmed]
PHST- 2020/02/06 06:00 [medline]
PHST- 2019/09/17 06:00 [entrez]
AID - 10.3892/ijmm.2019.4266 [doi]
PST - ppublish
SO  - Int J Mol Med. 2019 Sep;44(3):1151-1160. doi: 10.3892/ijmm.2019.4266. Epub 2019 
      Jul 5.