PMID- 26860701
OWN - NLM
STAT- MEDLINE
DCOM- 20160728
LR  - 20181113
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 344-346
DP  - 2016 Feb 17
TI  - Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases human hepatic 
      stellate cell activation.
PG  - 26-33
LID - S0300-483X(16)30012-9 [pii]
LID - 10.1016/j.tox.2016.02.001 [doi]
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a halogenated aromatic hydrocarbon 
      that elicits toxicity through the aryl hydrocarbon receptor (AhR). In the liver, 
      gross markers of TCDD toxicity are attributed to AhR activation in parenchymal 
      hepatocytes. However, less is known regarding the consequences of TCDD treatment 
      on non-parenchymal cells in the liver. Hepatic stellate cells (HSCs) are 
      non-parenchymal cells that store vitamin A when quiescent. Upon liver injury, 
      activated HSCs lose this storage ability and instead function in the development 
      and maintenance of inflammation and fibrosis through the production of 
      pro-inflammatory mediators and collagen type I. Reports that TCDD exposure 
      disrupts hepatic retinoid homeostasis and dysregulates extracellular matrix 
      remodeling in the liver led us to speculate that TCDD treatment may disrupt HSC 
      activity. The human HSC line LX-2 was used to test the hypothesis that TCDD 
      treatment directly activates HSCs. Results indicate that exposure to 10nM TCDD 
      almost completely inhibited lipid droplet storage in LX-2 cells cultured with 
      retinol and palmitic acid. TCDD treatment also increased LX-2 cell proliferation, 
      expression of alpha-smooth muscle actin, and production of monocyte chemoattractant 
      protein-1 (MCP-1), all of which are characteristics of activated HSCs. However, 
      TCDD treatment had no effect on Col1a1 mRNA levels in LX-2 cells stimulated with 
      the potent profibrogenic mediator, transforming growth factor-beta. The 
      TCDD-mediated increase in LX-2 cell proliferation, but not MCP-1 production, was 
      abolished when phosphoinositide 3-kinase was inhibited. These results indicate 
      that HSCs are susceptible to direct modulation by TCDD and that TCDD likely 
      increases HSC activation through a multi-faceted mechanism.
CI  - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved.
FAU - Harvey, Wendy A
AU  - Harvey WA
AD  - Department of Biological Sciences, Boise State University, Boise, ID 83725, 
      United States.
FAU - Jurgensen, Kimberly
AU  - Jurgensen K
AD  - Department of Biological Sciences, Boise State University, Boise, ID 83725, 
      United States.
FAU - Pu, Xinzhu
AU  - Pu X
AD  - Biomolecular Research Center, Boise State University, Boise, ID 83725, United 
      States.
FAU - Lamb, Cheri L
AU  - Lamb CL
AD  - Biomolecular Sciences Ph.D. Program, Boise State University, Boise, ID 83725, 
      United States.
FAU - Cornell, Kenneth A
AU  - Cornell KA
AD  - Biomolecular Research Center, Boise State University, Boise, ID 83725, United 
      States; Biomolecular Sciences Ph.D. Program, Boise State University, Boise, ID 
      83725, United States; Department of Chemistry and Biochemistry, Boise State 
      University, Boise, ID 83725, United States.
FAU - Clark, Reilly J
AU  - Clark RJ
AD  - Department of Biological Sciences, Boise State University, Boise, ID 83725, 
      United States.
FAU - Klocke, Carolyn
AU  - Klocke C
AD  - Department of Biological Sciences, Boise State University, Boise, ID 83725, 
      United States.
FAU - Mitchell, Kristen A
AU  - Mitchell KA
AD  - Department of Biological Sciences, Boise State University, Boise, ID 83725, 
      United States; Biomolecular Sciences Ph.D. Program, Boise State University, 
      Boise, ID 83725, United States. Electronic address: 
      kristenmitchell@boisestate.edu.
LA  - eng
GR  - R15DK08874/DK/NIDDK NIH HHS/United States
GR  - P20GM109095/GM/NIGMS NIH HHS/United States
GR  - P20 GM103408/GM/NIGMS NIH HHS/United States
GR  - P20 GM109095/GM/NIGMS NIH HHS/United States
GR  - P20GM103408/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20160206
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Receptors, Aryl Hydrocarbon)
SB  - IM
MH  - Cell Line
MH  - Cell Proliferation/*drug effects/physiology
MH  - Hepatic Stellate Cells/*drug effects/*metabolism
MH  - Humans
MH  - Polychlorinated Dibenzodioxins/*toxicity
MH  - Receptors, Aryl Hydrocarbon/agonists/metabolism
PMC - PMC4792734
MID - NIHMS760293
OTO - NOTNLM
OT  - Collagen
OT  - Hepatic stellate cell
OT  - Liver
OT  - MCP-1
OT  - TCDD
EDAT- 2016/02/11 06:00
MHDA- 2016/07/29 06:00
PMCR- 2017/02/17
CRDT- 2016/02/11 06:00
PHST- 2015/04/08 00:00 [received]
PHST- 2015/12/02 00:00 [revised]
PHST- 2016/02/04 00:00 [accepted]
PHST- 2016/02/11 06:00 [entrez]
PHST- 2016/02/11 06:00 [pubmed]
PHST- 2016/07/29 06:00 [medline]
PHST- 2017/02/17 00:00 [pmc-release]
AID - S0300-483X(16)30012-9 [pii]
AID - 10.1016/j.tox.2016.02.001 [doi]
PST - ppublish
SO  - Toxicology. 2016 Feb 17;344-346:26-33. doi: 10.1016/j.tox.2016.02.001. Epub 2016 
      Feb 6.