PMID- 18413412
OWN - NLM
STAT- MEDLINE
DCOM- 20080919
LR  - 20131121
IS  - 0961-2033 (Print)
IS  - 0961-2033 (Linking)
VI  - 17
IP  - 4
DP  - 2008 Apr
TI  - Rapamycin prevents the development of nephritis in lupus-prone NZB/W F1 mice.
PG  - 305-13
LID - 10.1177/0961203307088289 [doi]
AB  - Rapamycin is a potent immunosuppressive drug currently used mainly for rejection 
      prophylaxis in renal transplantation. The aim of this study was to determine the 
      effect of rapamycin treatment on the development of nephritis in lupus-prone New 
      Zealand Black/White F1 (NZB/W F1) mice. Twelve-week-old female NZB/W F1 mice were 
      treated with rapamycin (3 mg/kg body weight) or saline once daily by oral gavage 
      for 20 weeks. The severity of nephritis was assessed by clinical and biochemical 
      parameters, renal histology, immunohistochemistry and gene expression studies. 
      Rapamycin treatment markedly reduced proteinuria, improved renal function, 
      decreased serum anti-double stranded DNA antibody levels and diminished 
      splenomegaly. Kidney sections from saline-treated mice showed marked mesangial 
      proliferation, tubular dilation with protein cast deposition and interstitial 
      inflammatory cell infiltration. Rapamycin-treated mice had near normal renal 
      histology, with marked reduction in glomerular immune deposition and the 
      infiltration by T cells, B cells and macrophages. Rapamycin treatment was 
      associated with down-regulation of intra-renal expression of monocyte 
      chemoattractant protein-1 (MCP-1) mRNA and protein. We conclude that rapamycin is 
      highly effective in preventing the development of nephritis in NZB/W F1 mice. The 
      beneficial effects of rapamycin are mediated through inhibition of 
      lymphoproliferation and reduced MCP-1 expression.
FAU - Lui, S L
AU  - Lui SL
AD  - Department of Medicine, The University of Hong Kong, Tung Wah Hospital, Hong Kong 
      SAR, People's Republic of China.
FAU - Yung, S
AU  - Yung S
FAU - Tsang, R
AU  - Tsang R
FAU - Zhang, F
AU  - Zhang F
FAU - Chan, K W
AU  - Chan KW
FAU - Tam, S
AU  - Tam S
FAU - Chan, T M
AU  - Chan TM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Lupus
JT  - Lupus
JID - 9204265
RN  - 0 (Antibodies, Antinuclear)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (RNA, Messenger)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Antibodies, Antinuclear/immunology
MH  - Cell Proliferation/drug effects
MH  - Chemokine CCL2/biosynthesis/genetics
MH  - Cytokines
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Gene Expression
MH  - Immunohistochemistry
MH  - Immunosuppressive Agents/*administration & dosage
MH  - Kidney Glomerulus/immunology/metabolism/pathology
MH  - Lupus Nephritis/immunology/pathology/*prevention & control
MH  - Mice
MH  - Mice, Inbred NZB
MH  - RNA, Messenger/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sirolimus/*administration & dosage
MH  - T-Lymphocytes/immunology
EDAT- 2008/04/17 09:00
MHDA- 2008/09/20 09:00
CRDT- 2008/04/17 09:00
PHST- 2008/04/17 09:00 [pubmed]
PHST- 2008/09/20 09:00 [medline]
PHST- 2008/04/17 09:00 [entrez]
AID - 17/4/305 [pii]
AID - 10.1177/0961203307088289 [doi]
PST - ppublish
SO  - Lupus. 2008 Apr;17(4):305-13. doi: 10.1177/0961203307088289.