Interleukin 4 downregulates cell growth and prostaglandin release of human mesangial cells

Biochem Biophys Res Commun. 1993 Dec 15;197(2):486-93. doi: 10.1006/bbrc.1993.2505.

Abstract

Several clinical studies have proposed that a T cell derived cytokine IL-4 is operative in glomerulonephritis; however, its biological activities on renal cells have not been investigated. To elucidate its possible role in glomerulonephritis, we have examined whether IL-4 has effect on cell growth and prostaglandins synthesis using cultured mesangial cells (MC). IL-4 dose-dependently suppressed DNA synthesis and cell proliferation. IL-4 (10 ng/ml) alone did not affect prostaglandin E2 (PGE2) synthesis by mesangial cells, though, it inhibited IL-1 alpha- and TNF alpha-stimulated PGE2 synthesis by 48% and 81%, respectively. Comparable inhibition was observed on the conversion of exogenous arachidonic acid to PGs by IL-1-stimulated cells, suggesting IL-4 down regulates PG endoperoxide synthase activity. These results demonstrated that IL-4 is antagonistic to inflammatory cytokines upon PG synthesis as well as anti-mitogenic with MC.

MeSH terms

  • 6-Ketoprostaglandin F1 alpha / biosynthesis
  • Arachidonic Acid / metabolism
  • Cell Division / drug effects
  • Cells, Cultured
  • Dinoprostone / biosynthesis
  • Glomerular Mesangium / cytology*
  • Glomerular Mesangium / drug effects
  • Glomerular Mesangium / metabolism*
  • Glomerulonephritis / physiopathology
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-1 / pharmacology
  • Interleukin-4 / pharmacology*
  • Kinetics
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Prostaglandins / metabolism*
  • Recombinant Proteins / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Interleukin-1
  • Prostaglandins
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-4
  • Arachidonic Acid
  • 6-Ketoprostaglandin F1 alpha
  • Interferon-gamma
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone