PMID- 21633411
OWN - NLM
STAT- MEDLINE
DCOM- 20120214
LR  - 20220321
IS  - 1523-1755 (Electronic)
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 80
IP  - 5
DP  - 2011 Sep
TI  - Early interleukin 6 production by leukocytes during ischemic acute kidney injury 
      is regulated by TLR4.
PG  - 504-15
LID - 10.1038/ki.2011.140 [doi]
AB  - Although leukocytes infiltrate the kidney during ischemic acute kidney injury 
      (AKI) and release interleukin 6 (IL6), their mechanism of activation is unknown. 
      Here, we tested whether Toll-like receptor 4 (TLR4) on leukocytes mediated this 
      activation by interacting with high-mobility group protein B1 (HMGB1) released by 
      renal cells as a consequence of ischemic kidney injury. We constructed 
      radiation-induced bone marrow chimeras using C3H/HeJ and C57BL/10ScNJ strains of 
      TLR4 (-/-) mice and their respective TLR4 (+/+) wild-type counterparts and 
      studied them at 4 h after an ischemic insult. Leukocytes adopted from TLR4 (+/+) 
      mice infiltrated the kidneys of TLR4 (-/-) mice, and TLR4 (-/-) leukocytes 
      infiltrated the kidneys of TLR4 (+/+) mice but caused little functional renal 
      impairment in each case. Maximal ischemic AKI required both radiosensitive 
      leukocytes and radioresistant renal parenchymal and endothelial cells from TLR4 
      (+/+) mice. Only TLR4 (+/+) leukocytes produced IL6 in vivo and in response to 
      HMGB1 in vitro. Thus, following infiltration of the injured kidney, leukocytes 
      produce IL6 when their TLR4 receptors interact with HMGB1 released by injured 
      renal cells. This underscores the importance of TLR4 in the pathogenesis of 
      ischemic AKI.
FAU - Chen, Jianlin
AU  - Chen J
AD  - Division of Nephrology, Department of Internal Medicine, University of Texas 
      Southwestern Medical Center, Dallas, Texas 75390-8856, USA.
FAU - Hartono, John R
AU  - Hartono JR
FAU - John, Reji
AU  - John R
FAU - Bennett, Michael
AU  - Bennett M
FAU - Zhou, Xin Jin
AU  - Zhou XJ
FAU - Wang, Yanxia
AU  - Wang Y
FAU - Wu, Qingqing
AU  - Wu Q
FAU - Winterberg, Pamela D
AU  - Winterberg PD
FAU - Nagami, Glenn T
AU  - Nagami GT
FAU - Lu, Christopher Y
AU  - Lu CY
LA  - eng
GR  - F32 DK084701/DK/NIDDK NIH HHS/United States
GR  - DK079328/DK/NIDDK NIH HHS/United States
GR  - R0-1 DK069633/DK/NIDDK NIH HHS/United States
GR  - P30 DK079328/DK/NIDDK NIH HHS/United States
GR  - T32DK07257/DK/NIDDK NIH HHS/United States
GR  - F32DK084701/DK/NIDDK NIH HHS/United States
GR  - T32 DK007257/DK/NIDDK NIH HHS/United States
GR  - R01 DK069633/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110601
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (HMGB1 Protein)
RN  - 0 (Interleukin-6)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
CIN - Kidney Int. 2011 Sep;80(5):450-2. PMID: 21841835
MH  - Acute Kidney Injury/*immunology/pathology
MH  - Animals
MH  - Bone Marrow
MH  - Chemotaxis, Leukocyte
MH  - HMGB1 Protein/metabolism
MH  - Interleukin-6/*biosynthesis
MH  - Ischemia
MH  - Kidney
MH  - Leukocytes/*metabolism/physiology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Toll-Like Receptor 4/*physiology
PMC - PMC3394593
MID - NIHMS388027
EDAT- 2011/06/03 06:00
MHDA- 2012/02/15 06:00
PMCR- 2012/07/11
CRDT- 2011/06/03 06:00
PHST- 2011/06/03 06:00 [entrez]
PHST- 2011/06/03 06:00 [pubmed]
PHST- 2012/02/15 06:00 [medline]
PHST- 2012/07/11 00:00 [pmc-release]
AID - S0085-2538(15)55068-0 [pii]
AID - 10.1038/ki.2011.140 [doi]
PST - ppublish
SO  - Kidney Int. 2011 Sep;80(5):504-15. doi: 10.1038/ki.2011.140. Epub 2011 Jun 1.