PMID- 29601578
OWN - NLM
STAT- MEDLINE
DCOM- 20180709
LR  - 20181114
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 3
DP  - 2018
TI  - HIV induces production of IL-18 from intestinal epithelial cells that increases 
      intestinal permeability and microbial translocation.
PG  - e0194185
LID - 10.1371/journal.pone.0194185 [doi]
LID - e0194185
AB  - Interleukin-18 (IL-18) is a pleiotropic cytokine of the IL-1 family with multiple 
      context dependent functions. We and others have shown that HIV infection is 
      accompanied by increased circulating levels of IL-18 along with decreased levels 
      of its antagonist, Interleukin-18 Binding Protein (IL-18BP). The infection is 
      also accompanied by intestinal inflammation and decreased intestinal integrity as 
      measured by intestinal permeability, regeneration and repair. However, little is 
      known concerning the relation between high level of IL-18 associated with the 
      viral infection and intestinal permeability. Here we demonstrate that HIV 
      treatment increases production of IL-18 and decreases that of IL-18BP production 
      in human intestinal epithelial cell (IEC) lines. IL-18 causes apoptosis of the 
      IEC by activating caspase-1 and caspase-3. It induces epithelial barrier 
      hyperpermeability by decreasing and disrupting both tight and adherens junction 
      proteins, occludin, claudin 2 and beta-catenin. Disorganization of F-actin was 
      also observed in the IEC that were exposed to the cytokine. Moreover IL-18 
      decreases transepithelial electrical resistance (TEER) in Caco-2 and increases 
      permeability in HT29 monolayers. The cells' treatment with IL-18 causes an 
      increase in the expression of phosphorylated myosin II regulatory light-chain 
      (p-MLC) and myosin light-chain kinase (MLCK), and a decrease in phosphorylated 
      Signal Transducer and Activator of Transcription (p-STAT)-5. This increase in 
      p-MLC is suppressed by a Rho-kinase (ROCK)-specific inhibitor. Interestingly, the 
      levels of the cytokine correlate with those of LPS in the circulation in three 
      different categories of HIV infected patients (HAART-naive and HAART-treated 
      HIV-infected individuals, and Elite controls) as well as in healthy controls. 
      Collectively, these results suggest that the HIV-induced IL-18 plays a role in 
      increased intestinal permeability and microbial translocation observed in 
      HIV-infected individuals.
FAU - Allam, Ossama
AU  - Allam O
AD  - Laboratory of Innate Immunity, CHU Ste-Justine Research Center/Department of 
      Microbiology, Infectious Diseases & Immunology, University of Montreal, Montreal, 
      Quebec, Canada.
FAU - Samarani, Suzanne
AU  - Samarani S
AD  - Laboratory of Innate Immunity, CHU Ste-Justine Research Center/Department of 
      Microbiology, Infectious Diseases & Immunology, University of Montreal, Montreal, 
      Quebec, Canada.
FAU - Mehraj, Vikram
AU  - Mehraj V
AD  - Division of Hematology & Chronic Viral Illness Service, McGill University, 
      Montreal, Quebec, Canada.
FAU - Jenabian, Mohammad-Ali
AU  - Jenabian MA
AD  - Department of Biological Sciences, UQAM, Montreal, Quebec, Canada.
FAU - Tremblay, Cecile
AU  - Tremblay C
AD  - CHUM/ Department of Microbiology, Infectious Diseases & Immunology, University of 
      Montreal, Montreal, Quebec, Canada.
FAU - Routy, Jean-Pierre
AU  - Routy JP
AD  - Division of Hematology & Chronic Viral Illness Service, McGill University, 
      Montreal, Quebec, Canada.
FAU - Amre, Devendra
AU  - Amre D
AD  - CHU Ste-Justine Research Center/Department of Pediatrics, University of Montreal, 
      Montreal, Quebec, Canada.
FAU - Ahmad, Ali
AU  - Ahmad A
AUID- ORCID: 0000-0001-7689-7115
AD  - Laboratory of Innate Immunity, CHU Ste-Justine Research Center/Department of 
      Microbiology, Infectious Diseases & Immunology, University of Montreal, Montreal, 
      Quebec, Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180330
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Interleukin-18)
RN  - 0 (interleukin-18 binding protein)
SB  - IM
MH  - *Bacterial Translocation
MH  - Caco-2 Cells
MH  - Epithelial Cells/*metabolism/microbiology/pathology/virology
MH  - Female
MH  - HIV Infections/*metabolism/microbiology/pathology
MH  - HIV-1/*metabolism
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/metabolism
MH  - Interleukin-18/*biosynthesis
MH  - Intestinal Mucosa/*metabolism/microbiology/pathology/virology
MH  - Male
MH  - Permeability
PMC - PMC5877838
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2018/03/31 06:00
MHDA- 2018/07/10 06:00
PMCR- 2018/03/30
CRDT- 2018/03/31 06:00
PHST- 2017/06/19 00:00 [received]
PHST- 2018/02/26 00:00 [accepted]
PHST- 2018/03/31 06:00 [entrez]
PHST- 2018/03/31 06:00 [pubmed]
PHST- 2018/07/10 06:00 [medline]
PHST- 2018/03/30 00:00 [pmc-release]
AID - PONE-D-17-23252 [pii]
AID - 10.1371/journal.pone.0194185 [doi]
PST - epublish
SO  - PLoS One. 2018 Mar 30;13(3):e0194185. doi: 10.1371/journal.pone.0194185. 
      eCollection 2018.