Interleukin-1 beta down-regulates the oxytocin receptor in cultured uterine smooth muscle cells.

Abstract

Intrauterine infection accounts for 20% of preterm labor and results in the production of decidual inflammatory cytokines, including interleukin-1 (IL-1). The oxytocin receptor plays a key role in the onset of preterm labor. Cytokines likely regulate oxytocin receptor expression through several cytokine-induced DNA-binding proteins. The objective of this study was to evaluate the effect of the IL-1 alone on oxytocin receptor number as measured by radioligand binding and immunocytochemistry, and oxytocin receptor mRNA as measured by reverse transcriptase-polymerase chain reaction (RT-PCR) in cultured uterine myocytes. Unexpectedly, IL-1 treatment decreased oxytocin receptor number from 111,067 to 23,941 receptors/cell. Loss of oxytocin receptor binding began after 8 hr of IL-1 treatment and was reversible after IL-1 removal. Immunocytochemistry confirmed a loss of cellular oxytocin receptors. Oxytocin receptor mRNA decreased beginning after 2 hr of IL-1 treatment. IL-1 down-regulates the uterine oxytocin receptor in a time- and dose-dependent fashion.