PMID- 11012900
OWN - NLM
STAT- MEDLINE
DCOM- 20001113
LR  - 20061115
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 58
IP  - 4
DP  - 2000 Oct
TI  - Proinflammatory gene expression and macrophage recruitment in the rat remnant 
      kidney.
PG  - 1664-76
AB  - BACKGROUND: Macrophage (Mphi) infiltration may contribute to chronic renal 
      injury. We therefore sought to examine the expression of genes associated with 
      Mphi recruitment in the rat remnant kidney model. METHODS: Male Munich Wistar 
      rats underwent 5/6 nephrectomy or sham operation (SHM, N = 18) and received no 
      treatment (VEH, N = 18), enalapril 100 mg/L (ENA, N = 18), or candesartan 70 mg/L 
      (CSN, N = 24) in drinking water. Competitive, quantitative reverse 
      transcription-polymerase chain reaction was used to determine renal cortex mRNA 
      levels for cell adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and 
      intercellular adhesion molecule-1 (ICAM-1), the Mphi chemoattractant monocyte 
      chemoattractant protein-1 (MCP-1), Mphi products interleukin-1beta (IL-1beta) and 
      tumor necrosis factor-alpha (TNF-alpha), and the profibrotic cytokine 
      transforming growth factor-beta1 (TGF-beta1), at intervals post-nephrectomy. 
      RESULTS: Glomerular and interstitial Mphi infiltration in VEH rats was associated 
      with an early (4 week) and sustained rise in MCP-1 and TGF-beta1 mRNA levels. 
      Progressive increases in ICAM-1, VCAM-1, IL-1beta, and TNF-alpha expression 
      followed at 8 and 12 weeks. Immunostaining in VEH rats localized TGF-beta1 to 
      glomeruli, tubules, and interstitium; MCP-1 to tubules and interstitial cells; 
      ICAM-1 to glomeruli; and IL-1beta and TNF-alpha to tubules and interstitial 
      cells. At 12 weeks, both treatments normalized systolic blood pressure (ENA, 105 
      +/- 6; CSN, 97 +/- 3 mm Hg) and the urinary protein excretion rate (ENA, 8.4 +/- 
      0.9; CSN, 5.7 +/- 0.8 mg/day), prevented renal injury (focal and segmental 
      glomerulosclerosis: ENA, 3.3 +/- 0.9; CSN, 1.3 +/- 0.4%), and suppressed Mphi 
      infiltration and cytokine expression (with the exception of TNF-alpha) to near 
      SHM levels. CONCLUSIONS: These findings support the hypothesis that the 
      coordinated up-regulation of several molecules regulating Mphi recruitment and 
      activation is a fundamental response to renal mass ablation and is dependent on 
      an intact renin-angiotensin system. We speculate that these responses may play a 
      role in the pathogenesis of the ensuing glomerulosclerosis and tubulointerstitial 
      fibrosis.
FAU - Taal, M W
AU  - Taal MW
AD  - Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard 
      Medical School, Boston, Massachusetts 02115-6110, USA. mtaal@rics.bwh.harvard.edu
FAU - Zandi-Nejad, K
AU  - Zandi-Nejad K
FAU - Weening, B
AU  - Weening B
FAU - Shahsafaei, A
AU  - Shahsafaei A
FAU - Kato, S
AU  - Kato S
FAU - Lee, K W
AU  - Lee KW
FAU - Ziai, F
AU  - Ziai F
FAU - Jiang, T
AU  - Jiang T
FAU - Brenner, B M
AU  - Brenner BM
FAU - MacKenzie, H S
AU  - MacKenzie HS
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 (Chemokine CCL2)
RN  - 0 (DNA Primers)
RN  - 0 (Interleukin-1)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/genetics
MH  - DNA Primers
MH  - Gene Expression/immunology
MH  - Glomerulosclerosis, Focal Segmental/*immunology
MH  - Intercellular Adhesion Molecule-1/genetics
MH  - Interleukin-1/genetics
MH  - Kidney/cytology/immunology/surgery
MH  - Macrophages/*cytology/*immunology
MH  - Male
MH  - Nephrectomy
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Wistar
MH  - Renin-Angiotensin System/immunology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transforming Growth Factor beta/genetics
MH  - Tumor Necrosis Factor-alpha/genetics
MH  - Vascular Cell Adhesion Molecule-1/genetics
EDAT- 2000/09/30 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/09/30 11:00
PHST- 2000/09/30 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/09/30 11:00 [entrez]
AID - S0085-2538(15)47264-3 [pii]
AID - 10.1111/j.1523-1755.2000.00327.x [doi]
PST - ppublish
SO  - Kidney Int. 2000 Oct;58(4):1664-76. doi: 10.1111/j.1523-1755.2000.00327.x.