Valsartan inhibited the accumulation of dendritic cells in rat fibrotic renal tissue

Cell Mol Immunol. 2006 Jun;3(3):213-20.

Abstract

To observe the accumulation of dendritic cells (DCs) in rat remnant kidney and its contribution to tubulointerstitial fibrosis, under influence of valsartan on DCs, a rat remnant kidney model was established by subtotal nephrectomy. Four experimental groups were included: normal, sham, model (SNx) and the group treated with Valsartan (SNxV). Rats were killed at week 1, 4 and 12, respectively. CD1a+CD80+ DCs were assayed by double immunostaining method and the images were analyzed with Axioplan 2 microscopy. The expressions of P-selectin, TGF-beta1, alpha-SMA, collagen III and fibronectin was analyzed by immunohistochemistry or semi-quantitative RT-PCR, and the level of tubulointerstitial firosis (TIF) was scored. CD1a+CD80+ DCs were gradually increased among renal tubules, interstitium and vessels, especially in interstitium, and the number of DCs in model group at week 12 was much more than that in model groups at week 1 or 4. The expressions of P-selectin, TGF-beta1, alpha-SMA, collagen III and fibronectin in tubulointerstitial areas and the degree of TIF was increased substantially in model group at week 12. The accumulation of DCs in interstitium was well associated with the loss of renal function and the progression of tubulointerstitial fibrosis. Valsartan treatment inhibited the local accumulation of DCs and attenuated renal tubulointerstitial damage. The local DCs accumulation was related to tubulointerstitial fibrosis and renal dysfunction following renal ablation. Blockade to angiotensin II might be a potent way to attenuate renal immuno-inflammatory injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II Type 2 Receptor Blockers
  • Animals
  • Antihypertensive Agents / pharmacology*
  • Blood Pressure / drug effects
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology
  • Disease Models, Animal*
  • Disease Progression
  • Fibrosis
  • Immunohistochemistry
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / immunology
  • Kidney Diseases / pathology
  • Kidney Function Tests
  • Kidney Tubules / drug effects*
  • Kidney Tubules / pathology
  • Kidney Tubules / physiopathology
  • Membrane Glycoproteins / metabolism
  • Proteinuria / prevention & control
  • Rats
  • Rats, Sprague-Dawley
  • Tetrazoles / pharmacology*
  • Valine / analogs & derivatives*
  • Valine / pharmacology
  • Valsartan

Substances

  • Angiotensin II Type 2 Receptor Blockers
  • Antihypertensive Agents
  • Membrane Glycoproteins
  • Tetrazoles
  • Valsartan
  • Valine