Cytokine regulation of trophoblast steroidogenesis

Bruce B. Feinberg, Deborah J. Anderson, Michael A. Steller, V. Fülöp, Ross S. Berkowitz, Joseph A. Hill

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Activated monocytes and lymphocytes secrete cytokines that act as autocrine and paracrine mediators to promote and regulate local immune processes. These cell types are abundant at the maternal-fetal interface, and cytokines may play a role in pregnancy maintainance or failure. The purpose of this study was to determine the effects of selected monocyte- and lymphocyte-derived cytokines on trophoblast progesterone and estradiol production. JEG-3 choriocarcinoma cells were cultured in supplemented medium alone or in various concentrations of selected recombinant monocyte or lymphocyte cytokines. The cytokines were evaluated both individually and in combination. After 48 h of incubation, the culture supernatant was aspirated and stored at -20 C. Samples were then analyzed for steroid concentration by specific RIAs. Specific interleukin-1 (IL-1)- and tumor necrosis factor (TNF)-neutralizing antibodies were evaluated for their ability to abrogate the cytokine's observed stimulatory effect. To evaluate the physiological relevance of the progesterone-stimulating effect observed with monocyte- derived cytokines, JEG-3 cells were incubated with activated monocyte supernatant or directly cocultured with activated monocytes, and supernatants from these cultures were analyzed for progesterone levels. The monocyte cytokines (IL-1α (5 U/mL), IL-1β (5 U/mL), and TNFα (1000 U/mL)) significantly stimulated trophoblast progesterone production (nanograms per mL): JEG-3 control, 4.1 ± 0.5; IL-1α, 7.8 ± 0.9; IL-1β, 8.8 ± 0.5; and TNFα, 7.2 ± 0.8 (P <0.05). Neither the monocyte nor the lymphocyte cytokines altered trophoblast estradiol production. Activated monocyte supernatant and direct JEG-3-monocyte cocultures also significantly stimulated trophoblast progesterone production in vitro. The stimulatory effect of the monocyte-derived cytokines was specific, as demonstrated by neutralization assay. The increased trophoblast progesterone production was not due to enhanced cellular proliferation, but to enhanced cellular steroidogenesis, as measured by quantitative DNA analysis. The lymphocyte cytokines (IL-2, interferon-γ, and granulocyte-macrophage colony-stimulating factor had no effect on trophoblast progesterone production. We conclude that monocyte IL-1α, IL-1β, and TNFα may regulate trophoblast progesterone production through paracrine effects. Monocyte-trophoblast interactions may be significant in normal pregnancy as well as pregnancy disorders.

Original languageEnglish
Pages (from-to)586-591
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume78
Issue number3
DOIs
Publication statusPublished - Mar 1994

Fingerprint

Trophoblasts
Monocytes
Cytokines
Progesterone
Interleukin-1
Lymphocytes
Tumor Necrosis Factor-alpha
Interleukin-5
Estradiol
Pregnancy
Granulocyte-Macrophage Colony-Stimulating Factor
Choriocarcinoma
Neutralizing Antibodies
Interferons
Interleukin-2
Coculture Techniques
Assays
Steroids
Cultured Cells
Mothers

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Feinberg, B. B., Anderson, D. J., Steller, M. A., Fülöp, V., Berkowitz, R. S., & Hill, J. A. (1994). Cytokine regulation of trophoblast steroidogenesis. Journal of Clinical Endocrinology and Metabolism, 78(3), 586-591. https://doi.org/10.1210/jc.78.3.586

Cytokine regulation of trophoblast steroidogenesis. / Feinberg, Bruce B.; Anderson, Deborah J.; Steller, Michael A.; Fülöp, V.; Berkowitz, Ross S.; Hill, Joseph A.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 78, No. 3, 03.1994, p. 586-591.

Research output: Contribution to journalArticle

Feinberg, BB, Anderson, DJ, Steller, MA, Fülöp, V, Berkowitz, RS & Hill, JA 1994, 'Cytokine regulation of trophoblast steroidogenesis', Journal of Clinical Endocrinology and Metabolism, vol. 78, no. 3, pp. 586-591. https://doi.org/10.1210/jc.78.3.586
Feinberg, Bruce B. ; Anderson, Deborah J. ; Steller, Michael A. ; Fülöp, V. ; Berkowitz, Ross S. ; Hill, Joseph A. / Cytokine regulation of trophoblast steroidogenesis. In: Journal of Clinical Endocrinology and Metabolism. 1994 ; Vol. 78, No. 3. pp. 586-591.
@article{5892636140f94fd2b90aec66f06eb5a1,
title = "Cytokine regulation of trophoblast steroidogenesis",
abstract = "Activated monocytes and lymphocytes secrete cytokines that act as autocrine and paracrine mediators to promote and regulate local immune processes. These cell types are abundant at the maternal-fetal interface, and cytokines may play a role in pregnancy maintainance or failure. The purpose of this study was to determine the effects of selected monocyte- and lymphocyte-derived cytokines on trophoblast progesterone and estradiol production. JEG-3 choriocarcinoma cells were cultured in supplemented medium alone or in various concentrations of selected recombinant monocyte or lymphocyte cytokines. The cytokines were evaluated both individually and in combination. After 48 h of incubation, the culture supernatant was aspirated and stored at -20 C. Samples were then analyzed for steroid concentration by specific RIAs. Specific interleukin-1 (IL-1)- and tumor necrosis factor (TNF)-neutralizing antibodies were evaluated for their ability to abrogate the cytokine's observed stimulatory effect. To evaluate the physiological relevance of the progesterone-stimulating effect observed with monocyte- derived cytokines, JEG-3 cells were incubated with activated monocyte supernatant or directly cocultured with activated monocytes, and supernatants from these cultures were analyzed for progesterone levels. The monocyte cytokines (IL-1α (5 U/mL), IL-1β (5 U/mL), and TNFα (1000 U/mL)) significantly stimulated trophoblast progesterone production (nanograms per mL): JEG-3 control, 4.1 ± 0.5; IL-1α, 7.8 ± 0.9; IL-1β, 8.8 ± 0.5; and TNFα, 7.2 ± 0.8 (P <0.05). Neither the monocyte nor the lymphocyte cytokines altered trophoblast estradiol production. Activated monocyte supernatant and direct JEG-3-monocyte cocultures also significantly stimulated trophoblast progesterone production in vitro. The stimulatory effect of the monocyte-derived cytokines was specific, as demonstrated by neutralization assay. The increased trophoblast progesterone production was not due to enhanced cellular proliferation, but to enhanced cellular steroidogenesis, as measured by quantitative DNA analysis. The lymphocyte cytokines (IL-2, interferon-γ, and granulocyte-macrophage colony-stimulating factor had no effect on trophoblast progesterone production. We conclude that monocyte IL-1α, IL-1β, and TNFα may regulate trophoblast progesterone production through paracrine effects. Monocyte-trophoblast interactions may be significant in normal pregnancy as well as pregnancy disorders.",
author = "Feinberg, {Bruce B.} and Anderson, {Deborah J.} and Steller, {Michael A.} and V. F{\"u}l{\"o}p and Berkowitz, {Ross S.} and Hill, {Joseph A.}",
year = "1994",
month = "3",
doi = "10.1210/jc.78.3.586",
language = "English",
volume = "78",
pages = "586--591",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "3",

}

TY - JOUR

T1 - Cytokine regulation of trophoblast steroidogenesis

AU - Feinberg, Bruce B.

AU - Anderson, Deborah J.

AU - Steller, Michael A.

AU - Fülöp, V.

AU - Berkowitz, Ross S.

AU - Hill, Joseph A.

PY - 1994/3

Y1 - 1994/3

N2 - Activated monocytes and lymphocytes secrete cytokines that act as autocrine and paracrine mediators to promote and regulate local immune processes. These cell types are abundant at the maternal-fetal interface, and cytokines may play a role in pregnancy maintainance or failure. The purpose of this study was to determine the effects of selected monocyte- and lymphocyte-derived cytokines on trophoblast progesterone and estradiol production. JEG-3 choriocarcinoma cells were cultured in supplemented medium alone or in various concentrations of selected recombinant monocyte or lymphocyte cytokines. The cytokines were evaluated both individually and in combination. After 48 h of incubation, the culture supernatant was aspirated and stored at -20 C. Samples were then analyzed for steroid concentration by specific RIAs. Specific interleukin-1 (IL-1)- and tumor necrosis factor (TNF)-neutralizing antibodies were evaluated for their ability to abrogate the cytokine's observed stimulatory effect. To evaluate the physiological relevance of the progesterone-stimulating effect observed with monocyte- derived cytokines, JEG-3 cells were incubated with activated monocyte supernatant or directly cocultured with activated monocytes, and supernatants from these cultures were analyzed for progesterone levels. The monocyte cytokines (IL-1α (5 U/mL), IL-1β (5 U/mL), and TNFα (1000 U/mL)) significantly stimulated trophoblast progesterone production (nanograms per mL): JEG-3 control, 4.1 ± 0.5; IL-1α, 7.8 ± 0.9; IL-1β, 8.8 ± 0.5; and TNFα, 7.2 ± 0.8 (P <0.05). Neither the monocyte nor the lymphocyte cytokines altered trophoblast estradiol production. Activated monocyte supernatant and direct JEG-3-monocyte cocultures also significantly stimulated trophoblast progesterone production in vitro. The stimulatory effect of the monocyte-derived cytokines was specific, as demonstrated by neutralization assay. The increased trophoblast progesterone production was not due to enhanced cellular proliferation, but to enhanced cellular steroidogenesis, as measured by quantitative DNA analysis. The lymphocyte cytokines (IL-2, interferon-γ, and granulocyte-macrophage colony-stimulating factor had no effect on trophoblast progesterone production. We conclude that monocyte IL-1α, IL-1β, and TNFα may regulate trophoblast progesterone production through paracrine effects. Monocyte-trophoblast interactions may be significant in normal pregnancy as well as pregnancy disorders.

AB - Activated monocytes and lymphocytes secrete cytokines that act as autocrine and paracrine mediators to promote and regulate local immune processes. These cell types are abundant at the maternal-fetal interface, and cytokines may play a role in pregnancy maintainance or failure. The purpose of this study was to determine the effects of selected monocyte- and lymphocyte-derived cytokines on trophoblast progesterone and estradiol production. JEG-3 choriocarcinoma cells were cultured in supplemented medium alone or in various concentrations of selected recombinant monocyte or lymphocyte cytokines. The cytokines were evaluated both individually and in combination. After 48 h of incubation, the culture supernatant was aspirated and stored at -20 C. Samples were then analyzed for steroid concentration by specific RIAs. Specific interleukin-1 (IL-1)- and tumor necrosis factor (TNF)-neutralizing antibodies were evaluated for their ability to abrogate the cytokine's observed stimulatory effect. To evaluate the physiological relevance of the progesterone-stimulating effect observed with monocyte- derived cytokines, JEG-3 cells were incubated with activated monocyte supernatant or directly cocultured with activated monocytes, and supernatants from these cultures were analyzed for progesterone levels. The monocyte cytokines (IL-1α (5 U/mL), IL-1β (5 U/mL), and TNFα (1000 U/mL)) significantly stimulated trophoblast progesterone production (nanograms per mL): JEG-3 control, 4.1 ± 0.5; IL-1α, 7.8 ± 0.9; IL-1β, 8.8 ± 0.5; and TNFα, 7.2 ± 0.8 (P <0.05). Neither the monocyte nor the lymphocyte cytokines altered trophoblast estradiol production. Activated monocyte supernatant and direct JEG-3-monocyte cocultures also significantly stimulated trophoblast progesterone production in vitro. The stimulatory effect of the monocyte-derived cytokines was specific, as demonstrated by neutralization assay. The increased trophoblast progesterone production was not due to enhanced cellular proliferation, but to enhanced cellular steroidogenesis, as measured by quantitative DNA analysis. The lymphocyte cytokines (IL-2, interferon-γ, and granulocyte-macrophage colony-stimulating factor had no effect on trophoblast progesterone production. We conclude that monocyte IL-1α, IL-1β, and TNFα may regulate trophoblast progesterone production through paracrine effects. Monocyte-trophoblast interactions may be significant in normal pregnancy as well as pregnancy disorders.

UR - http://www.scopus.com/inward/record.url?scp=0028293593&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028293593&partnerID=8YFLogxK

U2 - 10.1210/jc.78.3.586

DO - 10.1210/jc.78.3.586

M3 - Article

C2 - 8126130

AN - SCOPUS:0028293593

VL - 78

SP - 586

EP - 591

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 3

ER -