Effect Of Catecholamines On Human Monocyte-Derived Dendritic Cells Migration And Its Mechanism

Objective:Impaired emigration of DCs has recently been considered to play important role in AS, yet risk factors and mechanism for regulating the emigration function of DCs during AS is unclear. We sought to study the effects of CAs on emigration function and chemokine receptor expression of DCs and its molecule mechanism.Methods:Monocytes were purified by immunomagnetic micro beads, and were induced into DCs. After stimulated with LPS with or without CAs, emigration function of DCs towards MIP-3 was tested by Transwell assay, expression of CCR7 was measured by FACS and PCR, and secretion cytokines were measured by ELISA. We also study the role of MARK and PAR using different signal inhabitor and receptor blocker.Results:Exposure of DCs to Catecholamine neither induces apoptosis nor alters maturation. in vitro, Catecholamine impairs the migration of human monocyte-derived DCs toward MIP-3 after LPS-stimulated DC maturation. EPI can significantly inhibit LPS-triggered upregulation of CCR7 expression in DC, while NE enhance CCR7 expression and increases IL-10 release. Administration ofβAR blocker reverses the effects of CAs on chemokine receptor expression and DC migration. EPI inhabited the phosphorylation of p38 MAPK and the phosphorylation of NF-κB in LPS-treated DCs.Conclusion:EPI inhibits the migration function of DCs through the down-regulation of CCR7, while NF-κB and p38-MAPK pathway may be involved in EPI-mediated effects on DCs. Impairment of DCs migration due to regulation of chemokine receptor expression by CAs may contribute, in part, to chronic stress induced AS.