Interleukin-10 and transforming growth factor-β inhibit amniochorion tumor necrosis factor-α production by contrasting mechanisms of action

Therapeutic implications in prematurity

S. J. Fortunato, Ramkumar Menon, S. J. Lombardi

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

OBJECTIVE: This study was designed to detect the regulatory effect of the immunoinhibitory cytokines interleukin-10 and transforming growth factor- β on the amniochorion production of tumor necrosis factor-α. STUDY DESIGN: Amniochorionic membranes were collected from women undergoing elective repeat cesarean section with no history of infection. Membranes were placed in organ explant culture for 48 hours and then stimulated with lipopolysaccharide (50 ng/ml), lipopolysaccharide plus interleukin-10 (50/50, 50/100 mg/ml), interleukin-10 (50 and 100 ng/ml), lipopolysaccharide plus transforming growth factor-β (50/50 and 50/100 ng/ml), and transforming growth factor-β (50 and 100 ng/ml). At the end of a 24-hour stimulation tissue samples were frozen for ribonucleic acid analysis and media samples were frozen for enzyme-linked immunosorbent assay. Quantitation of the messenger ribonucleic acid was accomplished by quantitative competitive polymerase chain reaction, and tumor necrosis factor-α protein was assayed by use of enzyme-linked immunosorbent assay. RESULTS: Lipopolysaccharide stimulation of fetal membranes produced approximately 60,000 molecules of tumor necrosis factor- α messenger ribonucleic acid, whereas control tissue produced none. Lipopolysaccharide plus interleukin-10 stimulation resulted in a dose- dependent decrease in tumor necrosis factor-α messenger ribonucleic production (transcriptional regulation) to 6000 (50/50) and 600 (50/100) molecules. Enzyme-linked immunosorbent assay performed on media samples from these experiments demonstrated a dose-dependent reduction in tumor necrosis factor-α peptide release. Stimulation of membranes with lipopolysaccharide plus transforming growth factor-β had minimal effects on tumor necrosis factor-α messenger ribonucleic acid and protein production compared with lipopolysaccharide-treated samples. Membranes stimulated with interleukin-10 alone showed no effect on messenger ribonucleic acid or protein levels and remained similar to the levels seen in control tissues. In the absence of lipopolysaccharide, transforming growth factor-β treatment produced a dramatic decrease in tumor necrosis factor-α peptide levels without affecting messenger ribonucleic acid levels. CONCLUSION: In the presence of a stimulatory agent, interleukin-10 down-regulates tumor necrosis factor-α release from cultured human amniochorionic membranes. Transforming growth factor-β seems to have some stimulatory effect on transcription, and no effect on translation was seen wan concurrent lipopolysaccharide stimulation. However, down-regulation of tumor necrosis factor-α peptide by transforming growth factor was seen in fetal membranes when not overridden by an inflammatory stimulant. This study suggests that interleukin-10 and transforming growth factor-β can regulate tumor necrosis factor-α release from amniochorion under different conditions and by a different mechanism.

Original languageEnglish (US)
Pages (from-to)803-809
Number of pages7
JournalAmerican Journal of Obstetrics and Gynecology
Volume177
Issue number4
StatePublished - 1997
Externally publishedYes

Fingerprint

Transforming Growth Factors
Interleukin-10
Lipopolysaccharides
Tumor Necrosis Factor-alpha
RNA
Membranes
Therapeutics
Extraembryonic Membranes
Enzyme-Linked Immunosorbent Assay
Peptides
Down-Regulation
Repeat Cesarean Section
Proteins
Organ Culture Techniques
Cytokines
Polymerase Chain Reaction

Keywords

  • Amniochorion
  • Interleukin-10 transforming growth factor
  • Prematurity
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynecology

Cite this

@article{e541f0dcb526431f941c28c635e21fa5,
title = "Interleukin-10 and transforming growth factor-β inhibit amniochorion tumor necrosis factor-α production by contrasting mechanisms of action: Therapeutic implications in prematurity",
abstract = "OBJECTIVE: This study was designed to detect the regulatory effect of the immunoinhibitory cytokines interleukin-10 and transforming growth factor- β on the amniochorion production of tumor necrosis factor-α. STUDY DESIGN: Amniochorionic membranes were collected from women undergoing elective repeat cesarean section with no history of infection. Membranes were placed in organ explant culture for 48 hours and then stimulated with lipopolysaccharide (50 ng/ml), lipopolysaccharide plus interleukin-10 (50/50, 50/100 mg/ml), interleukin-10 (50 and 100 ng/ml), lipopolysaccharide plus transforming growth factor-β (50/50 and 50/100 ng/ml), and transforming growth factor-β (50 and 100 ng/ml). At the end of a 24-hour stimulation tissue samples were frozen for ribonucleic acid analysis and media samples were frozen for enzyme-linked immunosorbent assay. Quantitation of the messenger ribonucleic acid was accomplished by quantitative competitive polymerase chain reaction, and tumor necrosis factor-α protein was assayed by use of enzyme-linked immunosorbent assay. RESULTS: Lipopolysaccharide stimulation of fetal membranes produced approximately 60,000 molecules of tumor necrosis factor- α messenger ribonucleic acid, whereas control tissue produced none. Lipopolysaccharide plus interleukin-10 stimulation resulted in a dose- dependent decrease in tumor necrosis factor-α messenger ribonucleic production (transcriptional regulation) to 6000 (50/50) and 600 (50/100) molecules. Enzyme-linked immunosorbent assay performed on media samples from these experiments demonstrated a dose-dependent reduction in tumor necrosis factor-α peptide release. Stimulation of membranes with lipopolysaccharide plus transforming growth factor-β had minimal effects on tumor necrosis factor-α messenger ribonucleic acid and protein production compared with lipopolysaccharide-treated samples. Membranes stimulated with interleukin-10 alone showed no effect on messenger ribonucleic acid or protein levels and remained similar to the levels seen in control tissues. In the absence of lipopolysaccharide, transforming growth factor-β treatment produced a dramatic decrease in tumor necrosis factor-α peptide levels without affecting messenger ribonucleic acid levels. CONCLUSION: In the presence of a stimulatory agent, interleukin-10 down-regulates tumor necrosis factor-α release from cultured human amniochorionic membranes. Transforming growth factor-β seems to have some stimulatory effect on transcription, and no effect on translation was seen wan concurrent lipopolysaccharide stimulation. However, down-regulation of tumor necrosis factor-α peptide by transforming growth factor was seen in fetal membranes when not overridden by an inflammatory stimulant. This study suggests that interleukin-10 and transforming growth factor-β can regulate tumor necrosis factor-α release from amniochorion under different conditions and by a different mechanism.",
keywords = "Amniochorion, Interleukin-10 transforming growth factor, Prematurity, Tumor necrosis factor",
author = "Fortunato, {S. J.} and Ramkumar Menon and Lombardi, {S. J.}",
year = "1997",
language = "English (US)",
volume = "177",
pages = "803--809",
journal = "American Journal of Obstetrics and Gynecology",
issn = "0002-9378",
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number = "4",

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TY - JOUR

T1 - Interleukin-10 and transforming growth factor-β inhibit amniochorion tumor necrosis factor-α production by contrasting mechanisms of action

T2 - Therapeutic implications in prematurity

AU - Fortunato, S. J.

AU - Menon, Ramkumar

AU - Lombardi, S. J.

PY - 1997

Y1 - 1997

N2 - OBJECTIVE: This study was designed to detect the regulatory effect of the immunoinhibitory cytokines interleukin-10 and transforming growth factor- β on the amniochorion production of tumor necrosis factor-α. STUDY DESIGN: Amniochorionic membranes were collected from women undergoing elective repeat cesarean section with no history of infection. Membranes were placed in organ explant culture for 48 hours and then stimulated with lipopolysaccharide (50 ng/ml), lipopolysaccharide plus interleukin-10 (50/50, 50/100 mg/ml), interleukin-10 (50 and 100 ng/ml), lipopolysaccharide plus transforming growth factor-β (50/50 and 50/100 ng/ml), and transforming growth factor-β (50 and 100 ng/ml). At the end of a 24-hour stimulation tissue samples were frozen for ribonucleic acid analysis and media samples were frozen for enzyme-linked immunosorbent assay. Quantitation of the messenger ribonucleic acid was accomplished by quantitative competitive polymerase chain reaction, and tumor necrosis factor-α protein was assayed by use of enzyme-linked immunosorbent assay. RESULTS: Lipopolysaccharide stimulation of fetal membranes produced approximately 60,000 molecules of tumor necrosis factor- α messenger ribonucleic acid, whereas control tissue produced none. Lipopolysaccharide plus interleukin-10 stimulation resulted in a dose- dependent decrease in tumor necrosis factor-α messenger ribonucleic production (transcriptional regulation) to 6000 (50/50) and 600 (50/100) molecules. Enzyme-linked immunosorbent assay performed on media samples from these experiments demonstrated a dose-dependent reduction in tumor necrosis factor-α peptide release. Stimulation of membranes with lipopolysaccharide plus transforming growth factor-β had minimal effects on tumor necrosis factor-α messenger ribonucleic acid and protein production compared with lipopolysaccharide-treated samples. Membranes stimulated with interleukin-10 alone showed no effect on messenger ribonucleic acid or protein levels and remained similar to the levels seen in control tissues. In the absence of lipopolysaccharide, transforming growth factor-β treatment produced a dramatic decrease in tumor necrosis factor-α peptide levels without affecting messenger ribonucleic acid levels. CONCLUSION: In the presence of a stimulatory agent, interleukin-10 down-regulates tumor necrosis factor-α release from cultured human amniochorionic membranes. Transforming growth factor-β seems to have some stimulatory effect on transcription, and no effect on translation was seen wan concurrent lipopolysaccharide stimulation. However, down-regulation of tumor necrosis factor-α peptide by transforming growth factor was seen in fetal membranes when not overridden by an inflammatory stimulant. This study suggests that interleukin-10 and transforming growth factor-β can regulate tumor necrosis factor-α release from amniochorion under different conditions and by a different mechanism.

AB - OBJECTIVE: This study was designed to detect the regulatory effect of the immunoinhibitory cytokines interleukin-10 and transforming growth factor- β on the amniochorion production of tumor necrosis factor-α. STUDY DESIGN: Amniochorionic membranes were collected from women undergoing elective repeat cesarean section with no history of infection. Membranes were placed in organ explant culture for 48 hours and then stimulated with lipopolysaccharide (50 ng/ml), lipopolysaccharide plus interleukin-10 (50/50, 50/100 mg/ml), interleukin-10 (50 and 100 ng/ml), lipopolysaccharide plus transforming growth factor-β (50/50 and 50/100 ng/ml), and transforming growth factor-β (50 and 100 ng/ml). At the end of a 24-hour stimulation tissue samples were frozen for ribonucleic acid analysis and media samples were frozen for enzyme-linked immunosorbent assay. Quantitation of the messenger ribonucleic acid was accomplished by quantitative competitive polymerase chain reaction, and tumor necrosis factor-α protein was assayed by use of enzyme-linked immunosorbent assay. RESULTS: Lipopolysaccharide stimulation of fetal membranes produced approximately 60,000 molecules of tumor necrosis factor- α messenger ribonucleic acid, whereas control tissue produced none. Lipopolysaccharide plus interleukin-10 stimulation resulted in a dose- dependent decrease in tumor necrosis factor-α messenger ribonucleic production (transcriptional regulation) to 6000 (50/50) and 600 (50/100) molecules. Enzyme-linked immunosorbent assay performed on media samples from these experiments demonstrated a dose-dependent reduction in tumor necrosis factor-α peptide release. Stimulation of membranes with lipopolysaccharide plus transforming growth factor-β had minimal effects on tumor necrosis factor-α messenger ribonucleic acid and protein production compared with lipopolysaccharide-treated samples. Membranes stimulated with interleukin-10 alone showed no effect on messenger ribonucleic acid or protein levels and remained similar to the levels seen in control tissues. In the absence of lipopolysaccharide, transforming growth factor-β treatment produced a dramatic decrease in tumor necrosis factor-α peptide levels without affecting messenger ribonucleic acid levels. CONCLUSION: In the presence of a stimulatory agent, interleukin-10 down-regulates tumor necrosis factor-α release from cultured human amniochorionic membranes. Transforming growth factor-β seems to have some stimulatory effect on transcription, and no effect on translation was seen wan concurrent lipopolysaccharide stimulation. However, down-regulation of tumor necrosis factor-α peptide by transforming growth factor was seen in fetal membranes when not overridden by an inflammatory stimulant. This study suggests that interleukin-10 and transforming growth factor-β can regulate tumor necrosis factor-α release from amniochorion under different conditions and by a different mechanism.

KW - Amniochorion

KW - Interleukin-10 transforming growth factor

KW - Prematurity

KW - Tumor necrosis factor

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M3 - Article

VL - 177

SP - 803

EP - 809

JO - American Journal of Obstetrics and Gynecology

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