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

• Published in: American journal of obstetrics and gynecology Vol. 179; no. 3; pp. 794 - 799
• Main Authors: Fortunato, Stephen J., Menon, Ramkumar, Lombardi, Salvatore J.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Mosby, Inc 01-09-1998; Elsevier
• Subjects: Amnion - drug effects; Amnion - metabolism; Biological and medical sciences; Chorioamnionitis - metabolism; Chorion - drug effects; Chorion - metabolism; cytokines; Diseases of mother, fetus and pregnancy; Dose-Response Relationship, Drug; Female; Gynecology. Andrology. Obstetrics; Humans; Interleukin-10; Interleukin-10 - pharmacology; interleukin-8; Interleukin-8 - genetics; Interleukin-8 - metabolism; Lipopolysaccharides - pharmacology; Medical sciences; Organ Culture Techniques; Polymerase Chain Reaction; Pregnancy; Pregnancy. Fetus. Placenta; preterm labor; Transcription, Genetic; transforming growth factor; Transforming Growth Factors - pharmacology; preterm labor; cytokines; Interleukin-10; transforming growth factor; interleukin-8; Human; Chorioamnionitis; Pregnancy disorders; Transforming growth factor; Cytokine; Chorion; Placenta diseases; In vitro; Polymerase chain reaction; Fetal diseases; Polypeptide; Interleukin 10; Amnion; Delivery disorders; Female; Influence; Molecular biology; Interleukin 8; Growth factor
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/S0002-9378(98)70085-7

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-β (50/50, 50/100), transforming growth factor-β (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 × 10
6 molecules per microliter of interleukin-8 messenger ribonucleic acid compared with 6 × 10
3 molecules per microliter in controls. Transforming growth factor-β alone and lipopolysaccharide plus transforming growth factor-β stimulation produced 6 × 10
5 and 6 × 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 × 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-β–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-β 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. (Am J Obstet Gynecol 1998;179:794-9.)