PMID- 34712238
OWN - NLM
STAT- MEDLINE
DCOM- 20220118
LR  - 20240226
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - NLRC5 Deficiency Deregulates Hepatic Inflammatory Response but Does Not Aggravate 
      Carbon Tetrachloride-Induced Liver Fibrosis.
PG  - 749646
LID - 10.3389/fimmu.2021.749646 [doi]
LID - 749646
AB  - The nucleotide-binding leucine-rich repeat-containing receptor (NLR) family 
      protein-5 (NLRC5) controls NF-kappaB activation and production of inflammatory 
      cytokines in certain cell types. NLRC5 is considered a potential regulator of 
      hepatic fibrogenic response due to its ability to inhibit hepatic stellate 
      activation in vitro. To test whether NLRC5 is critical to control liver fibrosis, 
      we treated wildtype and NLRC5-deficient mice with carbon tetrachloride (CCl(4)) 
      and assessed pathological changes in the liver. Serum alanine transaminase levels 
      and histopathology examination of liver sections revealed that NLRC5 deficiency 
      did not exacerbate CCl(4)-induced liver damage or inflammatory cell infiltration. 
      Sirius red staining of collagen fibers and hydroxyproline content showed 
      comparable levels of liver fibrosis in CCl(4)-treated NLRC5-deficient and control 
      mice. Myofibroblast differentiation and induction of collagen genes were 
      similarly increased in both groups. Strikingly, the fibrotic livers of 
      NLRC5-deficient mice showed reduced expression of matrix metalloproteinase-3 
      (Mmp3) and tissue inhibitor of MMPs-1 (Timp1) but not Mmp2 or Timp2. Fibrotic 
      livers of NLRC5-deficient mice had increased expression of TNF but similar 
      induction of TGFbeta compared to wildtype mice. CCl(4)-treated control and 
      NLRC5-deficient mice displayed similar upregulation of Cx3cr1, a monocyte 
      chemoattractant receptor gene, and the Cd68 macrophage marker. However, the 
      fibrotic livers of NLRC5-deficient mice showed increased expression of F4/80 
      (Adgre1), a marker of tissue-resident macrophages. NLRC5-deficient livers showed 
      increased phosphorylation of the NF-kappaB subunit p65 that remained elevated 
      following fibrosis induction. Taken together, NLRC5 deficiency deregulates 
      hepatic inflammatory response following chemical injury but does not 
      significantly aggravate the fibrogenic response, showing that NLRC5 is not a 
      critical regulator of liver fibrosis pathogenesis.
CI  - Copyright (c) 2021 Quenum, Shukla, Rexhepi, Cloutier, Ghosh, Kufer, Ramanathan and 
      Ilangumaran.
FAU - Quenum, Akouavi Julite I
AU  - Quenum AJI
AD  - Department of Immunology and Cell Biology, Faculty of Medicine and Health 
      Sciences, Universite de Sherbrooke, Sherbrooke, Canada.
FAU - Shukla, Akhil
AU  - Shukla A
AD  - Department of Immunology and Cell Biology, Faculty of Medicine and Health 
      Sciences, Universite de Sherbrooke, Sherbrooke, Canada.
FAU - Rexhepi, Fjolla
AU  - Rexhepi F
AD  - Department of Immunology and Cell Biology, Faculty of Medicine and Health 
      Sciences, Universite de Sherbrooke, Sherbrooke, Canada.
FAU - Cloutier, Maryse
AU  - Cloutier M
AD  - Department of Immunology and Cell Biology, Faculty of Medicine and Health 
      Sciences, Universite de Sherbrooke, Sherbrooke, Canada.
FAU - Ghosh, Amit
AU  - Ghosh A
AD  - Department of Immunology and Cell Biology, Faculty of Medicine and Health 
      Sciences, Universite de Sherbrooke, Sherbrooke, Canada.
FAU - Kufer, Thomas A
AU  - Kufer TA
AD  - Department of Immunology (180b), Institute of Nutritional Medicine, University of 
      Hohenheim, Stuttgart, Germany.
FAU - Ramanathan, Sheela
AU  - Ramanathan S
AD  - Department of Immunology and Cell Biology, Faculty of Medicine and Health 
      Sciences, Universite de Sherbrooke, Sherbrooke, Canada.
AD  - Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke (CR-CHUS), 
      Sherbrooke, Canada.
FAU - Ilangumaran, Subburaj
AU  - Ilangumaran S
AD  - Department of Immunology and Cell Biology, Faculty of Medicine and Health 
      Sciences, Universite de Sherbrooke, Sherbrooke, Canada.
AD  - Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke (CR-CHUS), 
      Sherbrooke, Canada.
LA  - eng
GR  - PJT-153255/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211012
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Cytokines)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (NLRC5 protein, mouse)
RN  - 0 (Transcription Factor RelA)
RN  - CL2T97X0V0 (Carbon Tetrachloride)
RN  - EC 2.6.1.2 (Alanine Transaminase)
SB  - IM
MH  - Alanine Transaminase/blood
MH  - Animals
MH  - Carbon Tetrachloride
MH  - Cytokines/blood/genetics/immunology
MH  - Gene Expression
MH  - Intracellular Signaling Peptides and Proteins/genetics/*immunology
MH  - Liver/immunology/pathology
MH  - Liver Cirrhosis/blood/genetics/*immunology/pathology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Transcription Factor RelA/immunology
MH  - Mice
PMC - PMC8546206
OTO - NOTNLM
OT  - NF-kappaB
OT  - NLRC5
OT  - carbon tetrachloride
OT  - hepatic stellate cells
OT  - liver fibrosis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/10/30 06:00
MHDA- 2022/01/19 06:00
PMCR- 2021/01/01
CRDT- 2021/10/29 06:25
PHST- 2021/07/29 00:00 [received]
PHST- 2021/09/27 00:00 [accepted]
PHST- 2021/10/29 06:25 [entrez]
PHST- 2021/10/30 06:00 [pubmed]
PHST- 2022/01/19 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.749646 [doi]
PST - epublish
SO  - Front Immunol. 2021 Oct 12;12:749646. doi: 10.3389/fimmu.2021.749646. eCollection 
      2021.