PMID- 24378685
OWN - NLM
STAT- MEDLINE
DCOM- 20140909
LR  - 20211203
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Linking)
VI  - 33
IP  - 3
DP  - 2014 Mar
TI  - Caffeic acid phenethyl ester attenuates pro-inflammatory and fibrogenic 
      phenotypes of LPS-stimulated hepatic stellate cells through the inhibition of 
      NF-kappaB signaling.
PG  - 687-94
LID - 10.3892/ijmm.2013.1613 [doi]
AB  - Hepatic stellate cells (HSCs) are the major cell type involved in liver fibrosis. 
      Lipopolysaccharide (LPS)-mediated signaling through Tauoll-like receptor 4 (TLR4) 
      in HSCs has been identified as a key event in liver fibrosis, and as the 
      molecular link between inflammation and liver fibrosis. In this study, we 
      investigated the effects of caffeic acid phenethyl ester (CAPE), one of the main 
      medicinal components of propolis, on the pro-inflammatory and fibrogenic 
      phenotypes of LPS-stimulated HSCs. HSCs from rats were isolated and cultured in 
      Dulbecco's modified Eagle's medium (DMEM). Following treatment with LPS, HSCs 
      showed a strong pro-inflammatory phenotype with an upregulation of 
      pro-inflammatory mediators, and a fibrogenic phenotype with enhanced collagen 
      synthesis, mediated by transforming growth factor-beta1 (TGF-beta1). CAPE significantly 
      and dose-dependently reduced LPS-induced nitrite production, as well as the 
      transcription and protein synthesis of monocyte chemoattractant protein-1 
      (MCP-1), interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS), as 
      determined by quantitative reverse transcription-polymerase chain reaction 
      (qRT-PCR), western blotting and enzyme-linked immunosorbent assays (ELISA). CAPE 
      further reduced the TGF-beta1-induced transcription and translation (protein 
      synthesis) of the gene coding for collagen type I alpha1 (col1A1), in LPS-stimulated 
      HSCs. Following LPS stimulation, the phosphorylation of the nuclear factor-kappaB 
      (NF-kappaB) inhibitor IkappaBalpha and consequently, the nuclear translocation of NF-kappaB, were 
      markedly increased in the HSCs, and these changes were reversed by pre-treatment 
      with CAPE. In conclusion, CAPE attenuates the pro-inflammatory phenotype of 
      LPS-stimulated HSCs, as well as the LPS-induced sensitization of HSCs to 
      fibrogenic cytokines by inhibiting NF-kappaB signaling. Our results provide new 
      insight into the treatment of hepatic fibrosis through regulation of the TLR4 
      signaling pathway.
FAU - Zhao, Wen-Xing
AU  - Zhao WX
AD  - Department of Pathology, Kunming General Hospital of PLA, Kunming, Yunnan 650032, 
      P.R. China.
FAU - Wang, Li
AU  - Wang L
AD  - Department of Pathology, Kunming General Hospital of PLA, Kunming, Yunnan 650032, 
      P.R. China.
FAU - Yang, Ju-Lun
AU  - Yang JL
AD  - Department of Pathology, Kunming General Hospital of PLA, Kunming, Yunnan 650032, 
      P.R. China.
FAU - Li, Lian-Zhen
AU  - Li LZ
AD  - School of Life Sciences of Yunnan University, Kunming, Yunnan 650091, P.R. China.
FAU - Xu, Wen-Mang
AU  - Xu WM
AD  - Department of Pathology, Kunming General Hospital of PLA, Kunming, Yunnan 650032, 
      P.R. China.
FAU - Li, Tao
AU  - Li T
AD  - Department of Pathology, Kunming General Hospital of PLA, Kunming, Yunnan 650032, 
      P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131230
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Caffeic Acids)
RN  - 0 (Collagen Type I)
RN  - 0 (Collagen Type I, alpha 1 Chain)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Transforming Growth Factor beta)
RN  - G960R9S5SK (caffeic acid phenethyl ester)
RN  - ML9LGA7468 (Phenylethyl Alcohol)
SB  - IM
MH  - Animals
MH  - Caffeic Acids/*administration & dosage
MH  - Collagen Type I/biosynthesis
MH  - Collagen Type I, alpha 1 Chain
MH  - Hepatic Stellate Cells/*drug effects/metabolism
MH  - Humans
MH  - Inflammation/chemically induced/drug therapy/*genetics/pathology
MH  - Lipopolysaccharides/administration & dosage
MH  - Liver Cirrhosis/chemically induced/drug therapy/*genetics/pathology
MH  - NF-kappa B/genetics
MH  - Phenylethyl Alcohol/administration & dosage/*analogs & derivatives
MH  - Rats
MH  - Signal Transduction/drug effects
MH  - Toll-Like Receptor 4
MH  - Transforming Growth Factor beta/biosynthesis
EDAT- 2014/01/01 06:00
MHDA- 2014/09/10 06:00
CRDT- 2014/01/01 06:00
PHST- 2013/08/21 00:00 [received]
PHST- 2013/12/05 00:00 [accepted]
PHST- 2014/01/01 06:00 [entrez]
PHST- 2014/01/01 06:00 [pubmed]
PHST- 2014/09/10 06:00 [medline]
AID - 10.3892/ijmm.2013.1613 [doi]
PST - ppublish
SO  - Int J Mol Med. 2014 Mar;33(3):687-94. doi: 10.3892/ijmm.2013.1613. Epub 2013 Dec 
      30.