Regulation of cyclooxygenase activity in cultured endometrial stromal cells by granulocyte-macrophage colony-stimulating factor.

ABSTRACT

OBJECTIVE: To assess the ability of granulocyte-macrophage colony-stimulating factor (GM-CSF) to regulate cyclooxygenase (COX) enzyme activity and prostaglandins (PGs) synthesis, specifically PGE2 production in stromal cells, neither of which have been addressed in the literature. DESIGN: Prospective study. SETTING: Department of obstetrics and gynecology at a university hospital. PATIENT(S) Human luteal phase endometrium was obtained from surgical specimens (n = 6) for clinical indications. INTERVENTION(S) Confluent stromal cells were stimulated with GM-CSF. MAIN OUTCOME MEASURE(S) Expression of COX mRNA, COX enzyme activity, and PGE2 level in cultured stromal cells. RESULT(S) Confluent stromal cell cultures treated with P and E2 for 9 days were stimulated with GM-CSF. After treatment of 12 hours, low-dose GM-CSF (0.001-0.1 ng/mL) increased COX-2 mRNA levels in stromal cell, whereas high dose GM-CSF (1-100 ng/mL) decreased COX-1 and COX-2 mRNA levels. After treatment of 48 hours, low concentrations of GM-CSF (0.001-0.1 ng/mL) increased total COX and COX-2 enzyme activity, whereas high concentrations of GM-CSF (1-100 ng/mL) inhibited COX and COX-2 activity; The PGE2 levels decreased by 31% to 393.3 pg/mL (P < .05) with concentrations of GM-CSF increasing from 1 ng/mL to 100 ng/mL. CONCLUSION(S) There appeared to be a biphasic pattern of COX-2 enzyme response to GM-CSF with low concentrations increasing activity and high concentrations inhibiting activity. It is possible that GM-CSF may provide critical regulation of PG production in the preimplantation period.