PMID- 27077596
OWN - NLM
STAT- MEDLINE
DCOM- 20170601
LR  - 20180105
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 100
IP  - 6
DP  - 2016 Jun
TI  - Toll-Like Receptor 4 Deficiency Improves Short-term Renal Function but not 
      Long-term Graft Survival in a Fully MHC-Mismatched Murine Model of Renal 
      Allograft Transplantation.
PG  - 1219-27
LID - 10.1097/TP.0000000000001168 [doi]
AB  - BACKGROUND: We have previously demonstrated that absence of myeloid 
      differentiation primary response gene 88 (MyD88) induced donor-specific kidney 
      allograft tolerance. The upstream pathways of MyD88 that mediate this process, 
      however, remain unclear. Toll-like receptor 4 (TLR4) is an innate immune receptor 
      that is dependent upon MyD88 for activity of its dominant signaling pathway. 
      Here, we investigated the role of TLR4 in kidney allograft rejection using a 
      fully major histocompatibility complex-mismatched, life-sustaining, murine model 
      of renal allograft rejection. METHODS: Donor (BALB/c) and recipient (C57BL/6) 
      mice either both deficient or sufficient for TLR4 underwent heterotopic renal 
      allograft transplantation, with an additional group of mice receiving renal 
      isografts as controls. Survival was assessed up to 100 days posttransplantation. 
      Animals were also sacrificed 14 days posttransplantation for assessment of the 
      acute allograft rejection response. RESULTS: Both wild-type (WT) and TLR4 
      allografts showed inferior survival compared to isografts, with no difference in 
      survival between the allograft groups. Serum creatinine was lower in TLR4 
      allografts at day 14 posttransplantation compared with WT allografts, but this 
      was not sustained by day 100. At day 14 posttransplant, increased CD11c dendritic 
      cell accumulation, expression of IL-2 and indoleamine 2,3-dioxygenase were 
      evident in TLR4 compared with WT allografts, whereas expression of inducible 
      nitric oxide synthase was decreased. CONCLUSIONS: Acute kidney allograft 
      rejection was modestly attenuated in TLR4 mice; however, long-term allograft 
      survival and function were not affected in our model. Protection against acute 
      rejection may involve increased accumulation of CD11c cells and indoleamine 
      2,3-dioxygenase expression.
FAU - Kwan, Tony K
AU  - Kwan TK
AD  - 1 Kidney Node Laboratory, The Charles Perkins Centre, Sydney Medical School, 
      University of Sydney, Sydney, Australia. 2 Renal Medicine, Royal Prince Alfred 
      Hospital, Sydney, Australia.
FAU - Chadban, Steven J
AU  - Chadban SJ
FAU - Wu, Huiling
AU  - Wu H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (CD11c Antigen)
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 0 (Interleukin-2)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - AYI8EX34EU (Creatinine)
SB  - IM
MH  - Allografts
MH  - Animals
MH  - CD11c Antigen/metabolism
MH  - Creatinine/blood
MH  - Disease Models, Animal
MH  - Graft Rejection
MH  - *Graft Survival
MH  - Immunity, Innate
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism
MH  - Interleukin-2/metabolism
MH  - *Kidney Transplantation
MH  - Macrophages/metabolism
MH  - Major Histocompatibility Complex/*immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Myeloid Differentiation Factor 88/metabolism
MH  - Signal Transduction
MH  - Toll-Like Receptor 4/*deficiency/genetics/metabolism
EDAT- 2016/04/15 06:00
MHDA- 2017/06/02 06:00
CRDT- 2016/04/15 06:00
PHST- 2016/04/15 06:00 [entrez]
PHST- 2016/04/15 06:00 [pubmed]
PHST- 2017/06/02 06:00 [medline]
AID - 10.1097/TP.0000000000001168 [doi]
PST - ppublish
SO  - Transplantation. 2016 Jun;100(6):1219-27. doi: 10.1097/TP.0000000000001168.