PMID- 10864580
OWN - NLM
STAT- MEDLINE
DCOM- 20000727
LR  - 20210511
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 11
IP  - 7
DP  - 2000 Jul
TI  - In vivo administration of a nuclear transcription factor-kappaB decoy suppresses 
      experimental crescentic glomerulonephritis.
PG  - 1244-1252
LID - 10.1681/ASN.V1171244 [doi]
AB  - Glomerular expression of cytokines, interleukin-1 (IL-1), and tumor necrosis 
      factor-alpha (TNF-alpha), together with leukocytic infiltration, are prominent 
      features in crescentic glomerulonephritis. Because these cytokines are targets 
      for nuclear transcription factor-kappaB (NF-kappaB), the use of NF-kappaB decoy 
      oligodeoxynucleotide (ODN) treatment was evaluated in an experimental disease 
      model. Crescentic glomerulonephritis was induced in primed Wistar rats by 
      injection of sheep antiglomerular basement membrane serum. Thirty minutes after 
      injection, rats were anesthetized and the left kidney was perfused with NF-kappaB 
      decoy ODN or scrambled ODN control mixed with a virus-liposome complex, and then 
      killed 7 d later. Animals given the scrambled control ODN developed severe 
      glomerulonephritis by day 7 with heavy proteinuria, glomerular crescents and 
      interstitial lesions, marked leukocytic infiltration, and upregulated renal 
      expression of cytokines (IL-1 and TNF-alpha) and adhesion molecules 
      (intercellular adhesion molecule-1). In contrast, NF-kappaB decoy ODN treatment 
      substantially inhibited the disease with a 50% reduction in proteinuria, a 
      threefold reduction in histologic damage, a 50% reduction in leukocytic 
      infiltration, and a 50 to 80% reduction in the renal expression of cytokines and 
      leukocyte adhesion molecules. In conclusion, this study has demonstrated that 
      NF-kappaB plays a key role in cytokine-mediated renal injury and that NF-kappaB 
      decoy ODN treatment has clear therapeutic potential in rapidly progressive 
      glomerulonephritis.
FAU - Tomita, Naruya
AU  - Tomita N
AD  - Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan.
FAU - Morishita, Ryuichi
AU  - Morishita R
AD  - Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan.
AD  - Gene Therapy Science, Osaka University Medical School, Suita, Japan.
FAU - Lan, Hui Y
AU  - Lan HY
AD  - Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia.
FAU - Yamamoto, Kei
AU  - Yamamoto K
AD  - Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan.
FAU - Hashizume, Masahide
AU  - Hashizume M
AD  - Dainippon Pharmaceutical Co., Ltd., Suita, Japan.
FAU - Notake, Mitsue
AU  - Notake M
AD  - Dainippon Pharmaceutical Co., Ltd., Suita, Japan.
FAU - Toyosawa, Kaoru
AU  - Toyosawa K
AD  - Dainippon Pharmaceutical Co., Ltd., Suita, Japan.
FAU - Fujitani, Buichi
AU  - Fujitani B
AD  - Dainippon Pharmaceutical Co., Ltd., Suita, Japan.
FAU - Mu, Wei
AU  - Mu W
AD  - Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia.
FAU - Nikolic-Paterson, David J
AU  - Nikolic-Paterson DJ
AD  - Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia.
FAU - Atkins, Robert C
AU  - Atkins RC
AD  - Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia.
FAU - Kaneda, Yasufumi
AU  - Kaneda Y
AD  - Gene Therapy Science, Osaka University Medical School, Suita, Japan.
FAU - Higaki, Jitsuo
AU  - Higaki J
AD  - Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan.
FAU - Ogihara, Toshio
AU  - Ogihara T
AD  - Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Cytokines)
RN  - 0 (Drug Carriers)
RN  - 0 (Liposomes)
RN  - 0 (NF-kappa B)
RN  - 0 (Oligonucleotides)
SB  - IM
MH  - Animals
MH  - Cell Movement/drug effects
MH  - Cytokines/antagonists & inhibitors/biosynthesis
MH  - Drug Carriers
MH  - Glomerulonephritis/*drug therapy/metabolism/pathology
MH  - Kidney/drug effects/metabolism/pathology
MH  - Leukocytes/physiology
MH  - Liposomes
MH  - Male
MH  - NF-kappa B/*genetics
MH  - Oligonucleotides/administration & dosage/genetics/*therapeutic use
MH  - Rats
MH  - Rats, Wistar
MH  - Respirovirus/genetics
MH  - Transfection
EDAT- 2000/06/23 11:00
MHDA- 2000/08/01 11:00
CRDT- 2000/06/23 11:00
PHST- 2000/06/23 11:00 [pubmed]
PHST- 2000/08/01 11:00 [medline]
PHST- 2000/06/23 11:00 [entrez]
AID - 11/7/1244 [pii]
AID - 10.1681/ASN.V1171244 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2000 Jul;11(7):1244-1252. doi: 10.1681/ASN.V1171244.