PMID- 26484872
OWN - NLM
STAT- MEDLINE
DCOM- 20160617
LR  - 20181202
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 10
DP  - 2015
TI  - Increased Sensitivity to Binge Alcohol-Induced Gut Leakiness and Inflammatory 
      Liver Disease in HIV Transgenic Rats.
PG  - e0140498
LID - 10.1371/journal.pone.0140498 [doi]
LID - e0140498
AB  - The mechanisms of alcohol-mediated advanced liver injury in HIV-infected 
      individuals are poorly understood. Thus, this study was aimed to investigate the 
      effect of binge alcohol on the inflammatory liver disease in HIV transgenic rats 
      as a model for simulating human conditions. Female wild-type (WT) or HIV 
      transgenic rats were treated with three consecutive doses of binge ethanol (EtOH) 
      (3.5 g/kg/dose oral gavages at 12-h intervals) or dextrose (Control). Blood and 
      liver tissues were collected at 1 or 6-h following the last dose of ethanol or 
      dextrose for the measurements of serum endotoxin and liver pathology, 
      respectively. Compared to the WT, the HIV rats showed increased sensitivity to 
      alcohol-mediated gut leakiness, hepatic steatosis and inflammation, as evidenced 
      with the significantly elevated levels of serum endotoxin, hepatic triglycerides, 
      histological fat accumulation and F4/80 staining. Real-time PCR analysis revealed 
      that hepatic levels of toll-like receptor-4 (TLR4), leptin and the downstream 
      target monocyte chemoattractant protein-1 (MCP-1) were significantly up-regulated 
      in the HIV-EtOH rats, compared to all other groups. Subsequent experiments with 
      primary cultured cells showed that both hepatocytes and hepatic Kupffer cells 
      were the sources of the elevated MCP-1 in HIV-EtOH rats. Further, TLR4 and MCP-1 
      were found to be upregulated by leptin. Collectively, these results show that HIV 
      rats, similar to HIV-infected people being treated with the highly active 
      anti-retroviral therapy (HAART), are more susceptible to binge alcohol-induced 
      gut leakiness and inflammatory liver disease than the corresponding WT, possibly 
      due to additive or synergistic interaction between binge alcohol exposure and HIV 
      infection. Based on these results, HIV transgenic rats can be used as a surrogate 
      model to study the molecular mechanisms of many disease states caused by heavy 
      alcohol intake in HIV-infected people on HAART.
FAU - Banerjee, Atrayee
AU  - Banerjee A
AD  - Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol 
      Abuse and Alcoholism, Bethesda, Maryland, United States of America.
FAU - Abdelmegeed, Mohamed A
AU  - Abdelmegeed MA
AD  - Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol 
      Abuse and Alcoholism, Bethesda, Maryland, United States of America.
FAU - Jang, Sehwan
AU  - Jang S
AD  - Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol 
      Abuse and Alcoholism, Bethesda, Maryland, United States of America.
FAU - Song, Byoung-Joon
AU  - Song BJ
AD  - Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol 
      Abuse and Alcoholism, Bethesda, Maryland, United States of America.
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20151020
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Leptin)
RN  - 0 (Toll-Like Receptor 4)
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Central Nervous System Depressants/toxicity
MH  - Chemokine CCL2/genetics/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Ethanol/*toxicity
MH  - Female
MH  - Gene Expression/drug effects
MH  - HIV/*genetics
MH  - HIV Infections/genetics/virology
MH  - Hepatocytes/drug effects/metabolism
MH  - Humans
MH  - Intestinal Diseases/chemically induced/*genetics/virology
MH  - Intestinal Mucosa/metabolism
MH  - Intestines/*drug effects/pathology
MH  - Leptin/genetics/metabolism
MH  - Liver Diseases, Alcoholic/etiology/*genetics/virology
MH  - Permeability/drug effects
MH  - Rats, Inbred F344
MH  - Rats, Transgenic
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Toll-Like Receptor 4/genetics/metabolism
PMC - PMC4618849
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/10/21 06:00
MHDA- 2016/06/18 06:00
PMCR- 2015/10/20
CRDT- 2015/10/21 06:00
PHST- 2015/06/25 00:00 [received]
PHST- 2015/09/25 00:00 [accepted]
PHST- 2015/10/21 06:00 [entrez]
PHST- 2015/10/21 06:00 [pubmed]
PHST- 2016/06/18 06:00 [medline]
PHST- 2015/10/20 00:00 [pmc-release]
AID - PONE-D-15-27745 [pii]
AID - 10.1371/journal.pone.0140498 [doi]
PST - epublish
SO  - PLoS One. 2015 Oct 20;10(10):e0140498. doi: 10.1371/journal.pone.0140498. 
      eCollection 2015.