Tsung-Hsuan Lai, Pi-Hui Wu, Wen-Bin Wua
Abstract
Chemokines were known to participate in inflammation and angiogenesis but have been recently rec-ognized to be involved in embryonic implantation and endometrium-related pathologies. Among thesechemokines, the CXC chemokines, such as CXCL1, have potential roles to work as biomarkers to iden-tify patients with uterine adenomyosis. In this study, human endometrial epithelial cells (HEECs) werederived from patients’ endometrium with adenomyosis. The inductive effects of CXCL1 production by var-ious mediators/growth factors were investigated in the HEECs. Of the tested mediators, VEGF was foundto be the most effective. The immunohistochemistry and RT-PCR analysis revealed a positive staining forVEGF and CXCL1 at the epithelium and the presence of CXCL1 in the human endometrium specimens,respectively. The CXCL1 induction by VEGF could be reduced by the antagonist for VEGF receptor (VEGFR),and by the inhibitors for NADPH oxidase and NF-B signaling pathway. However, it was not affected bysex hormones and the inhibitors for MAPKs, PI-3K, protein kinase A and C. In parallel, VEGF induced p47phox NADPH oxidase activation, IB phosphorylation, NF-B translocation and NF-B-DNA complexformation in the HEECs. Moreover, the CXCL1 released by the HEECs with VEGF stimulation attractedvascular endothelial cell migration. Taken together, we show that VEGF and CXCL1 are expressed inepithelium of the endometrium with adenomyosis and demonstrate here for the first time that VEGF iscapable of inducing CXCL1 expression in HEECs through VEGFR, p47 phox NADPH oxidase and NF-Bsignaling pathway, which is functionally required for attracting vascular endothelial cell migration.
Keywords:ChemokineCellular signalingGro-EndometriumEpithelial cellsNF-BVEGF
J Reprod Immunol. 2016 Nov;118:61-69. doi: 10.1016/j.jri.2016.08.011. Epub 2016 Sep 3. PMID: 27665197.
