Macrophage and epithelial cell H-ferritin expression regulates renal inflammation.

Academic Article

Abstract

  • Inflammation culminating in fibrosis contributes to progressive kidney disease. Cross-talk between the tubular epithelium and interstitial cells regulates inflammation by a coordinated release of cytokines and chemokines. Here we studied the role of heme oxygenase-1 (HO-1) and the heavy subunit of ferritin (FtH) in macrophage polarization and renal inflammation. Deficiency in HO-1 was associated with increased FtH expression, accumulation of macrophages with a dysregulated polarization profile, and increased fibrosis following unilateral ureteral obstruction in mice: a model of renal inflammation and fibrosis. Macrophage polarization in vitro was predominantly dependent on FtH expression in isolated bone marrow-derived mouse monocytes. Using transgenic mice with conditional deletion of FtH in the proximal tubules (FtH(PT-/-)) or myeloid cells (FtH(LysM-/-)), we found that myeloid FtH deficiency did not affect polarization or accumulation of macrophages in the injured kidney compared with wild-type (FtH(+/+)) controls. However, tubular FtH deletion led to a marked increase in proinflammatory macrophages. Furthermore, injured kidneys from FtH(PT-/-) mice expressed significantly higher levels of inflammatory chemokines and fibrosis compared with kidneys from FtH(+/+) and FtH(LysM-/-) mice. Thus, there are differential effects of FtH in macrophages and epithelial cells, which underscore the critical role of FtH in tubular-macrophage cross-talk during kidney injury.
  • Published In

    Keywords

  • Animals, Apoferritins, Cells, Cultured, Chemokine CCL2, Disease Models, Animal, Epithelial Cells, Fibrosis, Gene Expression, Heme Oxygenase-1, Interleukin-10, Interleukin-6, Kidney, Kidney Tubules, Proximal, Macrophage Activation, Macrophage Colony-Stimulating Factor, Macrophages, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Myeloid Cells, Nephritis, RNA, Messenger, Ureteral Obstruction
  • Digital Object Identifier (doi)

    Authorlist

  • Bolisetty S; Zarjou A; Hull TD; Traylor AM; Perianayagam A; Joseph R; Kamal AI; Arosio P; Soares MP; Jeney V
  • Start Page

  • 95
  • End Page

  • 108
  • Volume

  • 88
  • Issue

  • 1