Interleukin-1beta regulates vascular endothelial growth factor and soluble fms-like tyrosine kinase-1 secretion by human oviductal epithelial cells and stromal fibroblasts.

The aim of the present study was to evaluate the effects of interleukin (IL)-1beta on the production of vascular endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) in the human fallopian tube. Human oviductal epithelial cells (OECs) and oviductal stromal fibroblasts (OSFs) were isolated from ten premenopausal patients. The secretion of VEGF and sFlt-1 by cultured OECs and OSFs in response to IL-1beta and IL-1 receptor antagonist (IL-1RA) was measured using an enzyme-linked immunosorbent assay. The secretion of VEGF and sFlt-1 was detected in cultured OECs and OSFs under untreated conditions; secretion of these angiogenic modulators was significantly stimulated with IL-1beta administration in these cells. IL-1beta-induced production of VEGF and sFlt-1 by these cells was significantly inhibited by the addition of IL-1RA. The present findings suggest that IL-1beta in the local environment may stimulate oviductal vascular permeability by inducing the production of VEGF by oviductal cells via both autocrine and paracrine mechanisms. Simultaneous upregulation of sFlt-1 secretion by these cells after IL-1beta stimulation may prevent an excessive upregulation of vascular permeability. The modulation of the ratio of VEGF and sFlt-1 in the fallopian tube may contribute to the normal and pathological processes of oviductal fluid secretion by regulating oviductal vascular permeability during the menstrual cycle and during the peri-implantation period.