PMID- 15882261
OWN - NLM
STAT- MEDLINE
DCOM- 20050809
LR  - 20131121
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 67
IP  - 6
DP  - 2005 Jun
TI  - DNA vaccination with naked DNA encoding MCP-1 and RANTES protects against renal 
      injury in adriamycin nephropathy.
PG  - 2178-86
AB  - BACKGROUND: We have previously shown that monocyte chemoattractant protein-1 
      (MCP-1) and regulated upon activation, normal T-cell expressed and secreted 
      (RANTES) are significantly increased in renal cortex in adriamycin nephropathy. 
      In this study, we tested the effect of DNA vaccination encoding the C-C 
      chemokines MCP-1 and RANTES in a rat model of adriamycin nephropathy. METHODS: 
      Both reverse transcription-polymerase chain reaction (RT-PCR) products of MCP-1 
      and RANTES used as constructs were cloned into a pTarget vector for naked DNA 
      vaccination. Two hundred micrograms of DNA was injected into the tibialis 
      anterior muscle four times at weekly intervals. One week after the last DNA 
      vaccination, rats received adriamycin. All animals were sacrificed 4 weeks after 
      adriamycin administration. Changes in renal function and histologic features were 
      assessed. Enzyme-linked immunosorbent assay (ELISA) and Western blot were used 
      for autoantibody determination. Antibody specificity was assessed in in vitro 
      transmigration assays. RESULTS: Chemokine DNA vaccination significantly reduced 
      proteinuria (P < 0.05) and ameliorated creatinine clearance (P < 0.05) at 2, 3, 
      and 4 weeks after adriamycin administration. Morphometric analysis showed less 
      glomerular sclerosis (P < 0.001) and interstitial infiltrates (P < 0.005) in 
      chemokine DNA vaccination group compared with control groups. Anti-MCP-1 and 
      RANTES autoantibodies were detected in higher concentrations in chemokine DNA 
      vaccinated rats than in control rats (P < 0.001) and serum from vaccinated rats 
      blocked T-cell transmigration to MCP-1 and RANTES. CONCLUSION: In this study, we 
      have shown that naked DNA vaccination against MCP-1 and RANTES ameliorates the 
      progression of renal disease in the rat adriamycin nephropathy model of chronic 
      proteinuric renal disease. The protective mechanism may involve the production of 
      autoantibodies against MCP-1 and RANTES.
FAU - Wu, Huiling
AU  - Wu H
AD  - Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, New 
      South Wales, Australia. huilingw@med.usyd.edu.au
FAU - Wang, Yiping
AU  - Wang Y
FAU - Tay, Yuet-Ching
AU  - Tay YC
FAU - Zheng, Guoping
AU  - Zheng G
FAU - Zhang, Chun
AU  - Zhang C
FAU - Alexander, Stephen I
AU  - Alexander SI
FAU - Harris, David C H
AU  - Harris DC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Antibodies)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL5)
RN  - 0 (RNA, Messenger)
RN  - 0 (Vaccines, DNA)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - Animals
MH  - Antibodies/blood
MH  - Chemokine CCL2/genetics/*immunology
MH  - Chemokine CCL5/genetics/*immunology
MH  - Chemotaxis
MH  - Doxorubicin/*toxicity
MH  - Kidney/*drug effects
MH  - Male
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Wistar
MH  - Vaccination
MH  - Vaccines, DNA/*immunology
EDAT- 2005/05/11 09:00
MHDA- 2005/08/10 09:00
CRDT- 2005/05/11 09:00
PHST- 2005/05/11 09:00 [pubmed]
PHST- 2005/08/10 09:00 [medline]
PHST- 2005/05/11 09:00 [entrez]
AID - S0085-2538(15)50707-2 [pii]
AID - 10.1111/j.1523-1755.2005.00323.x [doi]
PST - ppublish
SO  - Kidney Int. 2005 Jun;67(6):2178-86. doi: 10.1111/j.1523-1755.2005.00323.x.