The induction of cyclooxygenase-2 by interleukin-4 in human umbilical vein endothelial cells: a possible role in regulation of fetal vascular tone.
OBJECTIVE: We sought to determine a possible role for interleukin-4 in the control of umbilical cord blood flow by evaluating its effect on cyclooxygenase-2 production of a vasoactive prostaglandin. STUDY DESIGN: Human umbilical vein endothelial cells in culture were incubated for 16 hours in media containing interleukin-4 in concentrations from 5 to 100 ng/ml. Prostaglandin E2 concentrations in the culture media were measured using a monoclonal enzyme-immunoassay. Concentrations of cyclooxygenase-1 and cyclooxygenase-2 were determined by Western blot analysis on cell homogenates. Statistical comparisons between prostaglandin E2, cyclooxygenase-1, and cyclooxygenase-2 concentrations for each interleukin-4 concentration were performed using a one way analysis of variance. RESULTS: Incubation of human umbilical vein endothelial cells in media containing interleukin-4 resulted in a significant increase in both prostaglandin E2 and cyclooxygenase-2 for interleukin-4 concentrations greater than 50 ng/ml (p < 0.05). Cyclooxygenase-1 levels were not affected. CONCLUSIONS: We suggest that interleukin-4 may have a role in the regulation of umbilical blood flow mediated through the induction of cyclooxygenase-2.