Glucocorticoids inhibit lipopolysaccharide-induced production of tumor necrosis factor-α by human fetal Kupffer cells

William H. Kutteh, William E. Rainey, Bruce R. Carr

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Inflammatory mediators, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα) are secreted by fixed tissue macrophages and exhibit local autocrine and paracrine effects as well as distant endocrine effects. Human fetal Kupffer cells, the fixed tissue macrophages of the liver, may play a role as modulators of immune and endocrine function in early embryonic and fetal development. In the present study we isolated human fetal Kupffer cells to greater than 90% purity and prepared short term cultures to investigate the effect of glucocorticoids on the secretion of the cytokine TNFα. Fetal Kupffer cells secreted TNFα and IL-1β after culture with bacterial lipopolysaccharide (LPS), indicating that these cells express mature macrophage function. Cortisol and dexamethasone dramatically suppressed the LPS-stimulated secretion of TNFα by fetal Kupffer cells. The inhibitory effects of glucocorticoids appeared to be specific, since estrogen, progesterone, and testosterone had no effect on LPS stimulation of TNFα production. None of the steroids tested altered basal production or enhanced the LPS-stimulated production of TNFα by fetal Kupffer cells. The inhibition by glucocorticoids could be reversed by the addition of RU 486, indicating that this effect was mediated by the glucocorticoid receptor. These results demonstrate that human fetal macrophages demonstrate mature macrophage function in early gestation; they can be activated to produce TNFα by a well characterized modulator of cellular function (LPS) and suppressed by glucocorticoids.

Original languageEnglish (US)
Pages (from-to)296-301
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume73
Issue number2
StatePublished - Aug 1991

Fingerprint

Kupffer Cells
Glucocorticoids
Lipopolysaccharides
Macrophages
Tumor Necrosis Factor-alpha
Interleukin-1
Modulators
Embryonic and Fetal Development
Tissue
Mifepristone
Glucocorticoid Receptors
human TNF protein
Liver
Dexamethasone
Progesterone
Hydrocortisone
Testosterone
Estrogens
Steroids
Cytokines

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Glucocorticoids inhibit lipopolysaccharide-induced production of tumor necrosis factor-α by human fetal Kupffer cells. / Kutteh, William H.; Rainey, William E.; Carr, Bruce R.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 73, No. 2, 08.1991, p. 296-301.

Research output: Contribution to journalArticle

@article{206de9c1f89649898f15f52978ea2cbb,
title = "Glucocorticoids inhibit lipopolysaccharide-induced production of tumor necrosis factor-α by human fetal Kupffer cells",
abstract = "Inflammatory mediators, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα) are secreted by fixed tissue macrophages and exhibit local autocrine and paracrine effects as well as distant endocrine effects. Human fetal Kupffer cells, the fixed tissue macrophages of the liver, may play a role as modulators of immune and endocrine function in early embryonic and fetal development. In the present study we isolated human fetal Kupffer cells to greater than 90{\%} purity and prepared short term cultures to investigate the effect of glucocorticoids on the secretion of the cytokine TNFα. Fetal Kupffer cells secreted TNFα and IL-1β after culture with bacterial lipopolysaccharide (LPS), indicating that these cells express mature macrophage function. Cortisol and dexamethasone dramatically suppressed the LPS-stimulated secretion of TNFα by fetal Kupffer cells. The inhibitory effects of glucocorticoids appeared to be specific, since estrogen, progesterone, and testosterone had no effect on LPS stimulation of TNFα production. None of the steroids tested altered basal production or enhanced the LPS-stimulated production of TNFα by fetal Kupffer cells. The inhibition by glucocorticoids could be reversed by the addition of RU 486, indicating that this effect was mediated by the glucocorticoid receptor. These results demonstrate that human fetal macrophages demonstrate mature macrophage function in early gestation; they can be activated to produce TNFα by a well characterized modulator of cellular function (LPS) and suppressed by glucocorticoids.",
author = "Kutteh, {William H.} and Rainey, {William E.} and Carr, {Bruce R.}",
year = "1991",
month = "8",
language = "English (US)",
volume = "73",
pages = "296--301",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "2",

}

TY - JOUR

T1 - Glucocorticoids inhibit lipopolysaccharide-induced production of tumor necrosis factor-α by human fetal Kupffer cells

AU - Kutteh, William H.

AU - Rainey, William E.

AU - Carr, Bruce R.

PY - 1991/8

Y1 - 1991/8

N2 - Inflammatory mediators, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα) are secreted by fixed tissue macrophages and exhibit local autocrine and paracrine effects as well as distant endocrine effects. Human fetal Kupffer cells, the fixed tissue macrophages of the liver, may play a role as modulators of immune and endocrine function in early embryonic and fetal development. In the present study we isolated human fetal Kupffer cells to greater than 90% purity and prepared short term cultures to investigate the effect of glucocorticoids on the secretion of the cytokine TNFα. Fetal Kupffer cells secreted TNFα and IL-1β after culture with bacterial lipopolysaccharide (LPS), indicating that these cells express mature macrophage function. Cortisol and dexamethasone dramatically suppressed the LPS-stimulated secretion of TNFα by fetal Kupffer cells. The inhibitory effects of glucocorticoids appeared to be specific, since estrogen, progesterone, and testosterone had no effect on LPS stimulation of TNFα production. None of the steroids tested altered basal production or enhanced the LPS-stimulated production of TNFα by fetal Kupffer cells. The inhibition by glucocorticoids could be reversed by the addition of RU 486, indicating that this effect was mediated by the glucocorticoid receptor. These results demonstrate that human fetal macrophages demonstrate mature macrophage function in early gestation; they can be activated to produce TNFα by a well characterized modulator of cellular function (LPS) and suppressed by glucocorticoids.

AB - Inflammatory mediators, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα) are secreted by fixed tissue macrophages and exhibit local autocrine and paracrine effects as well as distant endocrine effects. Human fetal Kupffer cells, the fixed tissue macrophages of the liver, may play a role as modulators of immune and endocrine function in early embryonic and fetal development. In the present study we isolated human fetal Kupffer cells to greater than 90% purity and prepared short term cultures to investigate the effect of glucocorticoids on the secretion of the cytokine TNFα. Fetal Kupffer cells secreted TNFα and IL-1β after culture with bacterial lipopolysaccharide (LPS), indicating that these cells express mature macrophage function. Cortisol and dexamethasone dramatically suppressed the LPS-stimulated secretion of TNFα by fetal Kupffer cells. The inhibitory effects of glucocorticoids appeared to be specific, since estrogen, progesterone, and testosterone had no effect on LPS stimulation of TNFα production. None of the steroids tested altered basal production or enhanced the LPS-stimulated production of TNFα by fetal Kupffer cells. The inhibition by glucocorticoids could be reversed by the addition of RU 486, indicating that this effect was mediated by the glucocorticoid receptor. These results demonstrate that human fetal macrophages demonstrate mature macrophage function in early gestation; they can be activated to produce TNFα by a well characterized modulator of cellular function (LPS) and suppressed by glucocorticoids.

UR - http://www.scopus.com/inward/record.url?scp=0025942807&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025942807&partnerID=8YFLogxK

M3 - Article

C2 - 1856261

AN - SCOPUS:0025942807

VL - 73

SP - 296

EP - 301

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 2

ER -