Regulation of LPS-induced molecules by progesterone in cultured human cervical fibroblasts under different treatment conditions

Objective:Wepreviously reported that progesterone (P4) treatment did not suppress LPS-induced upregulation of IL6 and IL8 in cultured human cervical fibroblasts. Here, we analyzed the expression of molecules associated with the pathophysiology of preterm labor under different levels of inflammatory stimulation (LPS stimulation) and/or the timing of progesterone treatment. Method of study: Human uterine cervical fibroblast cultures were established and incubated for 12h with 2.0 g/mL LPS (highLPS) or 0.2 g/ml LPS (low-LPS) in the presence or absence of 1.0 M P4 treated simultaneously or 1h prior to LPS stimulation (prior P4 treatment). Extracted cellular mRNA was subjected to real-time RT-PCR analyses to assess the expression of IL6, IL8, IL1beta, PTGS, MMP1 and hyaluronan synthase 2 (HAS2). Results: The expression of IL8 and IL6 stimulated with highLPS was not suppressed by simultaneous P4 treatment, but IL6 expressionwas significantly suppressed by prior P4 treatment. The expression of IL8 and IL6 stimulated with low-LPS was significantly suppressed by simultaneous and prior P4 treatment, and the suppression was more pronounced in prior P4 treatment. As an exception, HAS2 was not suppressed by P4 in any condition. Conclusion: Thus, early or prophylactic administration of progesterone prior to the overt preterm labor is considered important to reduce the risk of preterm birth.