Mesangial cells initiate compensatory renal tubular hypertrophy via IL-10-induced TGF-β secretion: Effect of the immunomodulator AS101 on this process

Inna Sinuani, Zhan Averbukh, Inna Gitelman, Micha J. Rapoport, Judit Sandbank, Michael Albeck, Benjamin Sredni, Joshua Weissgarten

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

The present study investigated the role of IL-10 produced by the mesangial cells in postnephrectomy compensatory renal growth and the effect of the immunomodulator AS101 on this process. One hundred forty unilateral nephrectomized and sham-operated male Sprague-Dawley rats were treated by AS101 or PBS before and after surgery. The results show that secretion of IL-10 and TGF-β by mesangial cells isolated from the remaining kidneys was increased significantly, compared with those of control and sham animals. Moreover, TGF-β secretion by mesangial cells was increased after the addition of exogenous recombinant IL-10 and inhibited in the presence of neutralizing anti-IL-10 antibodies. In vivo, compensatory growth of the remaining kidneys was associated with significant increase in IL-10 content in renal tissues and plasma. Immunohistochemical studies show that IL-10 was produced by mesangial cells. Elevated IL-10 levels were followed by the rise in TGF-β content in plasma and renal tissue. AS101 treatment decreased IL-10 and TGF-β expression in plasma and kidney tissues and results in 25% reduction in the fresh and fractional kidney weight and decreased hypertrophy of tubular cells (protein/DNA ratio, morphometric analysis). Taken together, these data demonstrate that TGF-β production by mesangial cells is IL-10 dependent. Mesangial cells are the major source of IL-10 in kidneys. AS101, by inhibiting the activity of IL-10, decreases TGF-β production by mesangial cells, thus limiting compensatory tubular cell hypertrophy.

Original languageEnglish
Pages (from-to)F384-F394
JournalAmerican Journal of Physiology - Renal Physiology
Volume291
Issue number2
DOIs
StatePublished - 4 Aug 2006

Keywords

  • Cytokines
  • Tubular cells
  • Unilateral nephrectomy

Fingerprint

Dive into the research topics of 'Mesangial cells initiate compensatory renal tubular hypertrophy via IL-10-induced TGF-β secretion: Effect of the immunomodulator AS101 on this process'. Together they form a unique fingerprint.

Cite this