PMID- 21703396
OWN - NLM
STAT- MEDLINE
DCOM- 20111028
LR  - 20211020
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 179
IP  - 1
DP  - 2011 Jul
TI  - Suppression of chronic damage in renal allografts by Liver X receptor (LXR) 
      activation relevant contribution of macrophage LXRalpha.
PG  - 92-103
LID - 10.1016/j.ajpath.2011.03.019 [doi]
AB  - Liver X receptors (LXR)-alpha,beta regulate intracellular cholesterol homeostasis and 
      inhibit inflammatory gene expression. We studied the effects of the 
      LXRalpha,beta-agonist GW3965 on acute and chronic organ damage in the F344-LEW rat 
      kidney transplantation model. In addition, to gain LXR isoform and cell-specific 
      insights BALB/c kidneys were transplanted into mice with macrophage 
      overexpression of LXRalpha (mLXRalpha-tg) and evaluated 7 and 42 days after 
      transplantation. After 56 days GW3965 improved significantly function and 
      morphology of rat kidney allografts by substantial reduction of mononuclear cell 
      infiltrate and fibrosis; in vitro GW3965 reduced inflammatory activity of bone 
      marrow-derived macrophages (BMDMs) and alloreactivity of T cells. Kidneys 
      transplanted into mLXRalpha-tg mice were also protected from development of chronic 
      allograft dysfunction. Similarly to GW3965-activated BMDMs, mLXRalpha-tg macrophages 
      secreted significantly less monocyte chemoattractant protein 1 and macrophage 
      inflammatory protein 1beta. Interestingly, 7 days after transplantation, when the 
      total number of intragraft macrophages did not differ, evidently more arginase 1- 
      and mannose receptor C type 1-positive cells were found in LXR rat and mice 
      kidney allografts; in vitro both LXR activation by GW3965 and mLXRalpha 
      overexpression accentuated the induction of alternative activation of BMDMs by 
      IL-4/IL-13, suggesting an additional mechanism by LXRs to prevent graft damage. 
      The results highlight the relevance of macrophage LXRalpha in allograft rejection and 
      prevention of fibrosis.
CI  - Copyright (c) 2011 American Society for Investigative Pathology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Kiss, Eva
AU  - Kiss E
AD  - Department of Cellular and Molecular Pathology, German Cancer Research Center, 
      Heidelberg, Germany.
FAU - Popovic, Zoran
AU  - Popovic Z
FAU - Bedke, Jens
AU  - Bedke J
FAU - Wang, Shijun
AU  - Wang S
FAU - Bonrouhi, Mahnaz
AU  - Bonrouhi M
FAU - Gretz, Norbert
AU  - Gretz N
FAU - Stettner, Paula
AU  - Stettner P
FAU - Teupser, Daniel
AU  - Teupser D
FAU - Thiery, Joachim
AU  - Thiery J
FAU - Porubsky, Stefan
AU  - Porubsky S
FAU - Adams, Judith
AU  - Adams J
FAU - Grone, Hermann-Josef
AU  - Grone HJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110505
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Benzoates)
RN  - 0 (Benzylamines)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (GW 3965)
RN  - 0 (Ligands)
RN  - 0 (Liver X Receptors)
RN  - 0 (Nr1h3 protein, mouse)
RN  - 0 (Nr1h3 protein, rat)
RN  - 0 (Orphan Nuclear Receptors)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Animals
MH  - Benzoates/*pharmacology
MH  - Benzylamines/*pharmacology
MH  - Blotting, Western
MH  - Chemokines/metabolism
MH  - Chronic Disease
MH  - Cytokines/metabolism
MH  - Fibrosis/metabolism/*prevention & control
MH  - Flow Cytometry
MH  - Graft Rejection/metabolism/*prevention & control
MH  - Immunoenzyme Techniques
MH  - Kidney Transplantation
MH  - Ligands
MH  - Liver X Receptors
MH  - Macrophages/*drug effects/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Orphan Nuclear Receptors/agonists/*metabolism
MH  - RNA, Messenger/genetics
MH  - Rats
MH  - Rats, Inbred F344
MH  - Rats, Inbred Lew
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transplantation, Homologous
PMC - PMC3123851
EDAT- 2011/06/28 06:00
MHDA- 2011/10/29 06:00
PMCR- 2012/07/01
CRDT- 2011/06/28 06:00
PHST- 2010/10/08 00:00 [received]
PHST- 2011/02/22 00:00 [revised]
PHST- 2011/03/17 00:00 [accepted]
PHST- 2011/06/28 06:00 [entrez]
PHST- 2011/06/28 06:00 [pubmed]
PHST- 2011/10/29 06:00 [medline]
PHST- 2012/07/01 00:00 [pmc-release]
AID - S0002-9440(11)00335-X [pii]
AID - AJPA354 [pii]
AID - 10.1016/j.ajpath.2011.03.019 [doi]
PST - ppublish
SO  - Am J Pathol. 2011 Jul;179(1):92-103. doi: 10.1016/j.ajpath.2011.03.019. Epub 2011 
      May 5.