Human CC chemokine CCL23 enhances expression of matrix metalloproteinase-2 and invasion of vascular endothelial cells
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Authors: Son, KN; Hwang, JS; Kwon, BS; Kim, JY
Abstract
Human CCL23 (also known as CK beta 8. MPIF-1, or MIP-3) has been recently reported to induce endothelial cell migration and tube formation via CCR1. Matrix metalloproteinases (MMPs) are involved in the degradation of the extracellular matrix and also appear to play critical roles in angiogenesis. In the present study, we have demonstrated that CCL23 enhances the expression of MMP-2 mRNA and protein levels in endothelial cells in a dose-dependent manner, but hits no effect on the expression levels of MMP-9, TlMP-1, TIMP2, and MT1-MMP. CCL23 was shown to dose-dependently activate the expression of the MMP-2/Lue reporter gene. thereby indicating that it stimulates the transcription of the MMP-2 gene. Vascular endothelial cells. when exposed to CCL23, showed it marked ability to invade through a 3D Matrigel. This increase in invasion was also correlated with enhancements in the expression and activity of MMP-2. Neutralization with anti-CCL23 and anti-CCR1 antibodies. its well as the heat-induced inactivation of CCL23, resulted in it blockage of the CCL23-activated invasion, indicating that the invasion of HUVECs was induced by CCL23 specifically. Futhermore, we showed that the CCL23-induced invasion was inhibited by MMP inhibitors such as GM6001 and a specific MMP-2 Inhibitor 1. Our results indicate that CCL23 may play a direct role in angiogenesis, via the upregulation of MMP-2 expression. (c) 2005 Elsevier Inc. All rights reserved.
Differential expression and functional roles of chemokine (C-C motif) ligand 23 and its receptor chemokine (C-C motif) receptor type 1 in the uterine endometrium during early pregnancy in pigs
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
Authors: Jeong, Wooyoung; Bae, Hyocheol; Lim, Whasun; Bazer, Fuller W.; Song, Gwonhwa
Abstract
Many chemokines expressed by cells of the uterine endometrium of mammals are involved in cell-cell interactions. However, little is known about expression and functional roles of chemokine (C-C motif) ligand 23 (CCL23) in the uterine endometrium. Results of this study demonstrated that CCL23 and its receptor, chemokine (C-C motif) receptor type 1 (CCR1), are up-regulated in porcine endometria during pregnancy. CCL23 and CCR1 mRNAs were strongly expressed in endometrial glandular (GE) and luminal (LE) epithelial cells. Treatment of porcine uterine luminal epithelial (pLE) cells with recombinant CCL23 increased the abundances of PCNA and cyclin D1, and enhanced proliferation and cell cycle progression in pLE cells. CCL23 also stimulated phosphorylation of cell signaling molecules including AKT and MAPKs in pLE cells. Furthermore, ER stress-related molecules were reduced by CCL23. These results suggest that CCL23-CCR1 signaling is important for endometrial development and establishment of pregnancy in pigs. (C) 2017 Elsevier Ltd. All rights reserved.