Mesangial cell-derived interleukin-10 modulates mesangial cell response to lipopolysaccharide

Am J Pathol. 1995 Jul;147(1):176-82.


Interleukin (IL)-10 is a novel cytokine produced by a variety of cells, including monocytes/macrophages, upon exposure to lipopolysaccharide (LPS). Recent observations indicate that, in turn, IL-10 exerts suppressive effects on macrophage response to LPS. Because mesangial cells are also a target for LPS, we have examined the potential role of IL-10 in the regulation of mesangial cell response to LPS. To this aim, we have studied the synthesis and the autocrine/paracrine function of IL-10 in cultured mouse mesangial cells. IL-10 mRNA expression and IL-10 protein secretion were determined by a reverse transcription polymerase chain reaction technique and a specific enzyme-linked immunosorbent assay, respectively. No IL-10 mRNA expression was detectable in unactivated cells. LPS induced IL-10 mRNA expression in a dose-dependent fashion (1 to 100 micrograms/ml). In addition, LPS induced IL-10 protein release that was both dose dependent (1 to 100 micrograms/ml) and time dependent (24 to 72 hours). We have also studied the effect of IL-10 on the production of inflammatory mediators by LPS-activated mouse mesangial cells. Whereas recombinant IL-10 inhibited the generation of tumor necrosis factor-alpha (TNF-alpha) and IL-1 beta by 90 and 60%, respectively, it did not affect the formation of nitric oxide-derived nitrite (NO2-) and nitrate (NO3-). As shown by the use of anti-IL-10 monoclonal antibody, endogenously produced IL-10 affected the generation of TNF-alpha but neither that of IL-1 beta nor that of NO2- and NO3-. Finally, we have examined whether conditions known to also reduce the generation of TNF-alpha modified the expression of IL-10. Of all the conditions tested, only the addition of desferrioxamine and transforming growth factor-beta were found to increase IL-10 release. Together, these data demonstrate that mesangial cell-derived IL-10 has important regulatory effects on the inflammatory response of these cells to LPS because of its capacity to blunt TNF-alpha generation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Cytokines / drug effects
  • DNA Primers / chemistry
  • Dose-Response Relationship, Drug
  • Escherichia coli*
  • Glomerular Mesangium / cytology
  • Glomerular Mesangium / drug effects
  • Glomerular Mesangium / metabolism*
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / pharmacology
  • Interleukin-10 / physiology*
  • Lipopolysaccharides / pharmacology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Molecular Sequence Data
  • Nitric Oxide / biosynthesis
  • Polymerase Chain Reaction
  • RNA, Messenger / biosynthesis
  • Recombinant Proteins
  • Transforming Growth Factor beta / pharmacology


  • Cytokines
  • DNA Primers
  • Lipopolysaccharides
  • RNA, Messenger
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Interleukin-10
  • Nitric Oxide