Cyclosporin A impairs dendritic cell migration by regulating chemokine receptor expression and inhibiting cyclooxygenase-2 expression

Migration of dendritic cells （DCs） into tissues and secondary lymphoid organs plays a crucial role in the initiation of innate and adaptive immunity. In this article, we show that eyelosporin A （CsA） impairs the migration of DCs both in vitro and in vivo. Exposure of DCs to clinical concentrations of CsA neither induces apoptosis nor alters development but does impair eytokine secretion, chemokine receptor expression, and migration. In vitro, CsA impairs the migration of mouse bone marrow-derived DCs toward maerophage inflammatory protein-3beta （MIP-3beta） and induces them to retain responsiveness to MIP-lalpha after lipopolysaecharide （LPS）-stimulated DC maturation, while in vivo administration of CsA inhibits the migration of DCs out of skin and into the secondary lymphoid organs. CsA impairs ehemokine receptor and cyelooxygenase-2 （COX- 2） expression normally triggered in LPS-stimulated DCs; administration of exogenous prostaglandin E2 （PGE2） reverses the effects of CsA on chemokine receptor expression and DC migration. Inhibition of nuclear faetor-kappaB （NF-kappaB） and mitogen-aetivated protein kinase （MAPK） pathway signaling by CsA may be responsible for the CsA-mediated effects on the regulation of ehemokine receptor and eyelooxygenase-2 （COX-2） expression. Impairment of DC migration due to inhibition of PGE2 production and regulation of ehemokine receptor expression may contribute, in part, to CsA-mediated immunosuppression.

Cyclosporin A impairs dendritic cell migration by regulating chemokine receptor expression and inhibiting cyclooxygenase-2 expression