title: Proinflammatory gene expression and macrophage recruitment in the rat remnant kidney.
abstract: 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.
authors.affiliation: Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115-6110, USA. mtaal@rics.bwh.harvard.edu
authors.forename: M W
authors.initials: MW
authors.lastname: Taal
authors.forename: K
authors.initials: K
authors.lastname: Zandi-Nejad
authors.forename: B
authors.initials: B
authors.lastname: Weening
authors.forename: A
authors.initials: A
authors.lastname: Shahsafaei
authors.forename: S
authors.initials: S
authors.lastname: Kato
authors.forename: K W
authors.initials: KW
authors.lastname: Lee
authors.forename: F
authors.initials: F
authors.lastname: Ziai
authors.forename: T
authors.initials: T
authors.lastname: Jiang
authors.forename: B M
authors.initials: BM
authors.lastname: Brenner
authors.forename: H S
authors.initials: HS
authors.lastname: MacKenzie
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics; D017931:DNA Primers; D015870:Gene Expression / Q000276:immunology; D005923:Glomerulosclerosis, Focal Segmental / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D007668:Kidney / Q000166:cytology / Q000276:immunology / Q000601:surgery; D008264:Macrophages / Q000166:cytology* / Q000276:immunology*; D008297:Male; D009392:Nephrectomy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
chemical_list: D018932:Chemokine CCL2; D017931:DNA Primers; D007375:Interleukin-1; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1