Sublytic C5b-9 induces IL-6 and TGF-β1 production by glomerular mesangial cells in rat Thy-1 nephritis through p300-mediated C/EBPβ acetylation

FASEB J. 2014 Mar;28(3):1511-25. doi: 10.1096/fj.13-242693. Epub 2013 Dec 16.


CCAAT/enhancer-binding protein (C/EBPβ)-enhanced IL-6 and TGF-β1 promoter activity and p300-mediated C/EBPβ acetylation were involved in up-regulation of IL-6 and TGF-β1 expression in GMCs attacked by sublytic C5b-9. In detail, the elements of C/EBPβ binding to rat IL-6 and TGF-β1 promoter and 3 acetylated sites of rat C/EBPβ protein were first revealed. Furthermore, silencing the p300 or C/EBPβ gene in rat kidney significantly reduced the production of IL-6 and TGF-β1 and renal lesions in Thy-1N rats. Together, these data indicate that the mechanism of IL-6 and TGF-β1 production in renal tissue of Thy-1N rats is associated with sublytic C5b-9 up-regulated p300 and p300-mediated C/EBPβ acetylation as well as C/EBPβ-activated IL-6 and TGF-β1 genes.

Keywords: post-translational modification; renal inflammation; renal pathology; transcription factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Base Sequence
  • CCAAT-Enhancer-Binding Protein-beta / metabolism*
  • Cells, Cultured
  • Complement Membrane Attack Complex / physiology*
  • DNA Primers
  • Glomerular Mesangium / cytology
  • Glomerular Mesangium / metabolism*
  • Interleukin-17 / biosynthesis
  • Interleukin-6 / biosynthesis*
  • Male
  • Nephritis / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Transforming Growth Factor beta1 / biosynthesis*
  • p300-CBP Transcription Factors / metabolism*


  • CCAAT-Enhancer-Binding Protein-beta
  • Complement Membrane Attack Complex
  • DNA Primers
  • Interleukin-17
  • Interleukin-6
  • Transforming Growth Factor beta1
  • p300-CBP Transcription Factors