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.
Nasu
Kaei
K
Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Idaigaoka, Oita, Japan. nasu@med.oita-u.ac.jp
Itoh
Hiroko
H
Yuge
Akitoshi
A
Kawano
Yasushi
Y
Yoshimatsu
Jun
J
Narahara
Hisashi
H
D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D010057:Oviducts / Q000187:drug effects* / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D012995:Solubility; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1; D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1