Silencing CX3CR1 production modulates the interaction between dendritic and endothelial cells.
CX3CR1, an important chemokine receptor in dendritic cells (DCs), is linked to the progression of atherosclerotic plaques. However, the mechanism(s) determining the role of CX3CR1 in atherosclerosis have not been clearly elucidated. In this study, we developed DCs from monocytes of Sprague-Dawley (SD) rats in the presence of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and recombinant human interleukin-4 (IL-4). The presence of recombinant human TNF-α and LPS forced the cells to mature. When compared to immature DCs, flow cytometry (FACS) analysis revealed that mature DCs display a sustained increase in the levels of CD11c, CD86, and CD80 expression. The expression of Fractalkine (FKN) in endothelial cells (ECs) contributes to the maturation of DCs and expression of CX3CR1. We revealed that mRNA expression levels of CX3CR1 in mature DCs are significantly higher than those of immature DCs (P<0.001). Transfection of DCs with siRNA specific for the CX3CR1 gene resulted in potent suppression of gene expression and inhibition of interactions between DCs and ECs. Based on these data, we hypothesized that CX3CR1 contributes to the DC-EC interaction. CX3CR1 may serve as a new target molecule for increasing therapeutic interactions in atherosclerosis.
Liu
Xiaoyan
X
Department of Pharmacy, Renji Hospital, Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Shanghai, 200127, China.
Lu
Guohong
G
Shen
Jinfang
J
D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D002448:Cell Adhesion; D002450:Cell Communication; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D008297:Male; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection
D000073883:CX3C Chemokine Receptor 1; C516305:CX3CR1 protein, rat; D034741:RNA, Small Interfering; D019707:Receptors, Chemokine