The effect of transforming growth factor and interleukin-10 on interleukin-8 release by human amniochorion may regulate histologic chorioamnionitis

Am J Obstet Gynecol. 1998 Sep;179(3 Pt 1):794-9. doi: 10.1016/s0002-9378(98)70085-7.

Abstract

Objective: Amniochorion is a source of interleukin-8 during infection and inflammation. In this study we investigate the role of 2 immunoinhibitory cytokines, transforming growth factor and interleukin-10, in regulating interleukin-8 production from human fetal membranes and define their mechanism of regulation.

Study design: Amniochorion was placed in an organ explant system for 72 hours. Tissues were stimulated with lipopolysaccharide (50 ng/mL), lipopolysaccharide plus transforming growth factor-beta (50/50, 50/100), transforming growth factor-beta (50 and 100 ng/mL), lipopolysaccharide plus interleukin-10 (50/50 and 50/100), and interleukin-10 (50 and 100 ng/mL) in culture. Tissue and media samples were frozen until quantitation of interleukin-8 messenger ribonucleic acid and protein. Quantitation of messenger ribonucleic acid was performed by quantitative competitive polymerase chain reaction and protein by enzyme-linked immunoassay, respectively.

Results: Lipopolysaccharide-stimulated tissues produced approximately 6 x 10(6) molecules per microliter of interleukin-8 messenger ribonucleic acid compared with 6 x 10(3) molecules per microliter in controls. Transforming growth factor-beta alone and lipopolysaccharide plus transforming growth factor-beta stimulation produced 6 x 10(5) and 6 x 10(4) molecules of interleukin-8 messenger ribonucleic acid per microliter, respectively. Tissues stimulated with lipopolysaccharide plus 50 ng/mL interleukin-10 produced approximately 600 molecules per microliter of interleukin-8 messenger ribonucleic acid, whereas no amplifiable messenger ribonucleic acid was detected in tissues treated with lipopolysaccharide plus 100 ng/mL interleukin-10. Tissues treated with interleukin-10 alone produced 6 x 10(3) molecules of messenger ribonucleic acid, similar to control levels. Enzyme-linked immunosorbent assay data showed similar levels of interleukin-8 peptide release from lipopolysaccharide and lipopolysaccharide plus transforming growth factor-beta-treated fetal membranes. A dose-dependent decrease in interleukin-8 peptide release was seen in tissues treated with lipopolysaccharide plus interleukin-10, whereas stimulation with transforming growth factor or interleukin-10 alone resulted in interleukin-8 peptide release similar to that of control levels.

Conclusion: Transforming growth factor-beta seems to have no effect on interleukin-8 protein production in the presence of an infectious agent; however, a drop in messenger ribonucleic acid levels was observed. Interleukin-10 in the presence of lipopolysaccharide showed down-regulation of interleukin-8 messenger ribonucleic acid expression and peptide production. These data suggest that fetal membrane interleukin-8 production can be controlled by interleukin-10 during an infectious process.

MeSH terms

  • Amnion / drug effects
  • Amnion / metabolism*
  • Chorioamnionitis / metabolism*
  • Chorion / drug effects
  • Chorion / metabolism*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Interleukin-10 / pharmacology*
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism*
  • Lipopolysaccharides / pharmacology
  • Organ Culture Techniques
  • Polymerase Chain Reaction
  • Pregnancy
  • Transcription, Genetic
  • Transforming Growth Factors / pharmacology*

Substances

  • Interleukin-8
  • Lipopolysaccharides
  • Interleukin-10
  • Transforming Growth Factors