PMID- 1856261
OWN - NLM
STAT- MEDLINE
DCOM- 19910827
LR  - 20131121
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 73
IP  - 2
DP  - 1991 Aug
TI  - Glucocorticoids inhibit lipopolysaccharide-induced production of tumor necrosis 
      factor-alpha by human fetal Kupffer cells.
PG  - 296-301
AB  - Inflammatory mediators, such as interleukin-1 beta (IL-1 beta) and tumor necrosis 
      factor-alpha (TNF alpha) 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 TNF alpha. Fetal 
      Kupffer cells secreted TNF alpha and IL-1 beta after culture with bacterial 
      lipopolysaccharide (LPS), indicating that these cells express mature macrophage 
      function. Cortisol and dexamethasone dramatically suppressed the LPS-stimulated 
      secretion of TNF alpha 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 TNF alpha production. None of 
      the steroids tested altered basal production or enhanced the LPS-stimulated 
      production of TNF alpha 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 TNF alpha by a well characterized modulator of 
      cellular function (LPS) and suppressed by glucocorticoids.
FAU - Kutteh, W H
AU  - Kutteh WH
AD  - Division of Reproductive Endocrinology, University of Texas Southwestern Medical 
      Center, Dallas 75235.
FAU - Rainey, W E
AU  - Rainey WE
FAU - Carr, B R
AU  - Carr BR
LA  - eng
GR  - HD-07190/HD/NICHD NIH HHS/United States
GR  - HD-1784/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Steroids)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 320T6RNW1F (Mifepristone)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Dexamethasone/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Fetus
MH  - Humans
MH  - Kinetics
MH  - Kupffer Cells/drug effects/*physiology
MH  - Lipopolysaccharides/antagonists & inhibitors/*pharmacology
MH  - Mifepristone/pharmacology
MH  - Steroids/pharmacology
MH  - Tumor Necrosis Factor-alpha/analysis/*biosynthesis
EDAT- 1991/08/01 00:00
MHDA- 1991/08/01 00:01
CRDT- 1991/08/01 00:00
PHST- 1991/08/01 00:00 [pubmed]
PHST- 1991/08/01 00:01 [medline]
PHST- 1991/08/01 00:00 [entrez]
AID - 10.1210/jcem-73-2-296 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1991 Aug;73(2):296-301. doi: 10.1210/jcem-73-2-296.