RGD Reference Report - DNA vaccination with naked DNA encoding MCP-1 and RANTES protects against renal injury in adriamycin nephropathy. - Rat Genome Database

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DNA vaccination with naked DNA encoding MCP-1 and RANTES protects against renal injury in adriamycin nephropathy.

Authors: Wu, H  Wang, Y  Tay, YC  Zheng, G  Zhang, C  Alexander, SI  Harris, DC 
Citation: Wu H, etal., Kidney Int. 2005 Jun;67(6):2178-86.
RGD ID: 2307176
Pubmed: PMID:15882261   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1523-1755.2005.00323.x   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
kidney disease  ISOCcl2 (Rattus norvegicus)2307176; 2307176 RGD 
kidney disease  ISOCcl5 (Rattus norvegicus)2307176; 2307176 RGD 
kidney disease  IMP 2307176; 2307176 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccl2  (C-C motif chemokine ligand 2)
Ccl5  (C-C motif chemokine ligand 5)

Genes (Mus musculus)
Ccl2  (C-C motif chemokine ligand 2)
Ccl5  (C-C motif chemokine ligand 5)

Genes (Homo sapiens)
CCL2  (C-C motif chemokine ligand 2)
CCL5  (C-C motif chemokine ligand 5)

Objects referenced in this article
Gene CCL13 C-C motif chemokine ligand 13 Homo sapiens

Additional Information