Diltiazem impairs maturation and functions of human dendritic cells.
The aim of this study was to define the effects of diltiazem, a calcium antagonist drug used in cardiology and in clinical transplantation, on the differentiation and maturation of human dendritic cells (DC). Herein, we demonstrate that diltiazem, in association with granulocyte macrophage-colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4), induces monocytes to differentiate into cells with many of the characteristic of DC. However, diltiazem-induced DC express high levels of mannose receptor and Fc gamma RII and, consequently, manifest a higher endocytic activity compared with GM-CSF+IL-4-induced DC. Importantly, diltiazem-induced DCs have an impaired responsiveness to lipopolysaccharide and CD40 ligand because they produce decreased levels of IL-12 and reveal a reduced ability to stimulate alloreactive T-cell responses as well as in inducing interferon-gamma producing Th1 cells. These effects may contribute to a decreased DC-dependent T-cell activation and may help to explain the immunoregulatory function of diltiazem and its effectiveness in preventing transplant rejection.
Bachetoni
Alessandra
A
Dipartimento di Chirurgia Generale P.Stefanini, Università La Sapienza, Rome, Italy. alessandra.bachetoni@uniroma1.it
D'Ambrosio
Antonella
A
Mariani
Paola
P
Cortesini
Raffaello
R
Quintieri
Francesca
F
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D004110:Diltiazem / Q000494:pharmacology*; D015536:Down-Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D018417:Th1 Cells / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects
D000276:Adjuvants, Immunologic; D018664:Interleukin-12; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004110:Diltiazem