PMID- 20136795
OWN - NLM
STAT- MEDLINE
DCOM- 20101019
LR  - 20100628
IS  - 1748-1716 (Electronic)
IS  - 1748-1708 (Linking)
VI  - 199
IP  - 3
DP  - 2010 Jul 1
TI  - TRAF6 knockdown promotes survival and inhibits inflammatory response to 
      lipopolysaccharides in rat primary renal proximal tubule cells.
PG  - 339-46
LID - 10.1111/j.1748-1716.2010.02097.x [doi]
AB  - AIM: TRAF6 is a unique adaptor protein of the tumour necrosis factor 
      receptor-associated factor family that mediates both tumour necrosis factor 
      receptor (TNFR) and interleukin-1 receptor/Toll-like receptor (IL-1R/TLR) 
      signalling. Activation of IL-1R/TLR and TNFR pathways in renal tubular cells 
      contributes to renal injury. This study aimed to investigate if blockade of 
      lipopolysaccharide (LPS)-triggered TLR4 signalling by small interfering RNA 
      (siRNA) targeting TRAF6 protects survival and inhibits inflammatory response in 
      isolated rat renal proximal tubular cells (PTCs). METHODS: PTCs isolated from 
      F344 rat kidneys were transfected with chemically synthesized siRNA targeting 
      TRAF6 mRNA. Real-time quantitative PCR was applied to measure mRNA level of 
      TRAF6, TNF-alpha, IL-6 and monocyte chemoattractant protein-1 (MCP-1). Protein 
      levels of extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase 
      (JNK), p38 mitogen-activated protein kinase, caspase 3 and cleaved caspase 3 were 
      evaluated by Western blotting. Cell viability was analysed with XTT reagents. 
      RESULTS: We found that the TRAF6 gene was effectively silenced in PTCs using 
      siRNA. TRAF6 knockdown resulted in reduced TNF-alpha and IL-6 mRNA expression 
      upon LPS challenge. LPS-induced phosphorylation of JNK and p38 was attenuated in 
      TRAF6 siRNA-transfected cells while the change in the phosphorylation of ERK was 
      not remarkable. TRAF6 knockdown was associated with increased cell viability and 
      reduced protein level of cleaved caspase-3, both, in the absence and presence of 
      LPS. CONCLUSION: Our studies suggest that TRAF6 knockdown may inhibit 
      inflammatory response and promote cell survival upon LPS challenge in primary rat 
      proximal renal tubular cells.
FAU - Liu, S
AU  - Liu S
AD  - Department of Nephrology, Technical University Munich, Germany.
FAU - Lutz, J
AU  - Lutz J
FAU - Chang, J
AU  - Chang J
FAU - Liu, D
AU  - Liu D
FAU - Heemann, U
AU  - Heemann U
FAU - Baumann, M
AU  - Baumann M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100205
PL  - England
TA  - Acta Physiol (Oxf)
JT  - Acta physiologica (Oxford, England)
JID - 101262545
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (TNF Receptor-Associated Factor 6)
RN  - 0 (Tlr4 protein, rat)
RN  - 0 (Toll-Like Receptor 4)
RN  - 63231-63-0 (RNA)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Animals, Genetically Modified
MH  - Blotting, Western
MH  - Cell Separation
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Inflammation/chemically induced/*genetics/*pathology
MH  - Kidney Tubules, Proximal/cytology/*pathology
MH  - Lipopolysaccharides/*toxicity
MH  - Male
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Phosphorylation
MH  - RNA/biosynthesis/genetics
MH  - RNA, Small Interfering
MH  - Rats
MH  - Rats, Inbred F344
MH  - Signal Transduction/drug effects/genetics
MH  - TNF Receptor-Associated Factor 6/*genetics/*physiology
MH  - Toll-Like Receptor 4/genetics
EDAT- 2010/02/09 06:00
MHDA- 2010/10/20 06:00
CRDT- 2010/02/09 06:00
PHST- 2010/02/09 06:00 [entrez]
PHST- 2010/02/09 06:00 [pubmed]
PHST- 2010/10/20 06:00 [medline]
AID - APS2097 [pii]
AID - 10.1111/j.1748-1716.2010.02097.x [doi]
PST - ppublish
SO  - Acta Physiol (Oxf). 2010 Jul 1;199(3):339-46. doi: 
      10.1111/j.1748-1716.2010.02097.x. Epub 2010 Feb 5.