Human decidual cell Toll-like receptor signaling in response to endotoxin: the effect of progestins.
OBJECTIVE
The purpose of this study was to determine whether progesterone, 17-alpha-hydroxyprogesterone, and 17-alpha hydroxyprogesterone caproate modulate the Toll-like receptor (TLR) pathway in the response of decidua to lipopolysaccharide.


METHODS
Cultured human decidual cells were incubated under control conditions, lipopolysaccharide alone, or pretreatment with each of the 3 progestins. Relative expression of 113 genes in the TLR pathway was determined by microarray.


RESULTS
We failed to demonstrate a suppression of TLR gene pathway expression in human decidual cells in response to lipopolysaccharide when the cells are pretreated with progestins. Pretreatment with each progestin before lipopolysaccharide resulted in a relative increase in the expression of the proapoptotic molecule, CASP8. There were no differences among the progestins.


CONCLUSIONS
Our data do not support suppression of TLR pathways as a mechanism for the benefit of 17-alpha hydroxyprogesterone caproate. Increased CASP8 gene expression raises the possibility that progestins "prime" the decidual cell to respond with a NFkappaB-mediated inflammatory response.
Simhan
Hyagriv N
HN
Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Chiao
Jye-Ping
JP
Mattison
Donald R
DR
Caritis
Steve N
SN
D002478:Cells, Cultured; D003656:Decidua / Q000166:cytology / Q000187:drug effects*; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D011247:Pregnancy; D011336:Probability; D011372:Progestins / Q000494:pharmacology*; D012016:Reference Values; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D004731:Endotoxins; D008070:Lipopolysaccharides; D011372:Progestins; D051193:Toll-Like Receptors