PMID- 18373668
OWN - NLM
STAT- MEDLINE
DCOM- 20081010
LR  - 20211020
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Print)
IS  - 0019-2805 (Linking)
VI  - 125
IP  - 1
DP  - 2008 Sep
TI  - Toll-like receptor-4-mediated macrophage activation is differentially regulated 
      by progesterone via the glucocorticoid and progesterone receptors.
PG  - 59-69
LID - 10.1111/j.1365-2567.2008.02820.x [doi]
AB  - Macrophage function has been demonstrated to be subject to modulation by 
      progesterone. However, as this steroid hormone can act through the glucocorticoid 
      receptor as well as the progesterone receptor, the mechanism of action has not 
      been precisely characterized. To determine the mode of action, we compared the 
      ability of progesterone, norgestrel (a synthetic progesterone-receptor-specific 
      agonist) and dexamethasone (a synthetic glucocorticoid receptor agonist) to 
      modulate macrophage function following stimulation of the Toll-like receptor-4 
      (TLR-4) ligand lipopolysaccharide (LPS). The results demonstrate that following 
      stimulation of TLR-4 with LPS and cotreatment with either progesterone or 
      dexamethasone, but not norgestrel, there is a significant reduction in nitric 
      oxide (NO) production, indicating that this progesterone-mediated effect is 
      through ligation of the glucocorticoid receptor. In contrast, LPS-induced 
      interleukin-12 (IL-12) production could be downregulated by all three steroids, 
      indicating that ligation by progesterone of either the glucocorticoid or the 
      progesterone receptors or both could mediate this effect. While progesterone 
      downmodulated NO-mediated killing of Leishmania donovani by activated macrophages 
      in vitro, most probably via the glucocorticoid receptor, it had little effect on 
      Toxoplasma gondii growth in these cells. This would suggest that 
      progesterone-mediated increased susceptibility to T. gondii during pregnancy is 
      more likely to be related to the ability of the hormone to downregulate IL-12 
      production and a type-1 response utilizing the progesterone as well as the 
      glucocorticoid receptors.
FAU - Jones, Leigh A
AU  - Jones LA
AD  - Strathclyde Institute for Pharmacy and Biomedical Sciences, University of 
      Strathclyde, Glasgow, UK.
FAU - Anthony, Jean-Paul
AU  - Anthony JP
FAU - Henriquez, Fiona L
AU  - Henriquez FL
FAU - Lyons, Russell E
AU  - Lyons RE
FAU - Nickdel, Mohammad B
AU  - Nickdel MB
FAU - Carter, Katharine C
AU  - Carter KC
FAU - Alexander, James
AU  - Alexander J
FAU - Roberts, Craig W
AU  - Roberts CW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080328
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Nitrites)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 0 (Receptors, Progesterone)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 187348-17-0 (Interleukin-12)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 3J8Q1747Z2 (Norgestrel)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Animals
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Dexamethasone/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation/drug effects
MH  - Hematopoietic Stem Cells/immunology
MH  - Interleukin-12/biosynthesis
MH  - Leishmania donovani
MH  - Leishmaniasis, Visceral/immunology
MH  - Lipopolysaccharides/immunology
MH  - Macrophage Activation/*immunology
MH  - Macrophages/immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Nitric Oxide/biosynthesis
MH  - Nitrites/metabolism
MH  - Norgestrel/pharmacology
MH  - Progesterone/*immunology
MH  - Receptors, Glucocorticoid/*immunology
MH  - Receptors, Progesterone/*immunology
MH  - Toll-Like Receptor 4/*immunology
MH  - Toxoplasmosis/immunology
PMC - PMC2526260
EDAT- 2008/04/01 09:00
MHDA- 2008/10/11 09:00
PMCR- 2009/09/01
CRDT- 2008/04/01 09:00
PHST- 2008/04/01 09:00 [pubmed]
PHST- 2008/10/11 09:00 [medline]
PHST- 2008/04/01 09:00 [entrez]
PHST- 2009/09/01 00:00 [pmc-release]
AID - IMM2820 [pii]
AID - 10.1111/j.1365-2567.2008.02820.x [doi]
PST - ppublish
SO  - Immunology. 2008 Sep;125(1):59-69. doi: 10.1111/j.1365-2567.2008.02820.x. Epub 
      2008 Mar 28.