Human decidual cell Toll-like receptor signaling in response to endotoxin: the effect of progestins.

Abstract

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. 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. 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. 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.