Apolipoprotein A-I induces IL-10 and PGE2 production in human monocytes and inhibits dendritic cell differentiation and maturation

https://doi.org/10.1016/j.bbrc.2005.10.065Get rights and content

Abstract

Apolipoprotein A-I (apoA-I), the major protein component of serum high-density lipoprotein, exhibits anti-inflammatory activity in atherosclerosis. In this study, we demonstrate that apoA-I inhibits DC differentiation and maturation. DC differentiated from monocytes in the presence of apoA-I showed a decreased expression of surface molecules such as CD1a, CD80, CD86, and HLA-DR. In addition, these DC exhibited decreased endocytic activity and weakened allogeneic T-cell activation. During DC differentiation in the presence of apoA-I, PGE2 and IL-10, which are known to be DC differentiation inhibitors and/or modulators of DC function, were produced at remarkable rates, whereas IL-12 production in the cells after stimulation with CD40 mAb and IFN-γ was significantly decreased in comparison with the control DC. T cells stimulated by apoA-I-pretreated DC produced significantly low levels of IFN-γ, and apoA-I inhibited cross-talk between DC and NK cells, in terms of IL-12 and IFN-γ production. Therefore, apoA-I appears to play an important role in modulating both innate immune response and inflammatory response. The novel inhibitory function of apoA-I on DC differentiation and function may facilitate the development of new therapeutic interventions in inflammatory diseases.

Section snippets

Materials and methods

Reagents for cell culture, cytokines, and antibodies. All cultures were incubated in RPMI 1640 medium (Sigma, St. Louis, MO) supplemented with 10% fetal bovine serum (FBS; Gibco, Grand Island, NY). The growth factors used in the primary cultures of DC precursors were recombinant human granulocyte–macrophage colony-stimulating factor (rhGM-CSF; provided by LG Biotech, Iksan, South Korea) and rhIL-4 (R&D Systems, Minneapolis, MN). Flow cytometric analysis for the determination of surface antigen

Apolipoprotein A-I impairs dendritic cell differentiation of monocytes

We attempted to determine whether or not the treatment of monocytes with apolipoprotein A-I (apoA-I) would affect their differentiation into dendritic cells (DC), in the presence of GM-CSF and IL-4. When antigen expressions were assessed by FACS analysis, CD1a expression on apoA-I-treated cells was appeared to have dramatically decreased in comparison with control DC, whereas CD14 expression in apoA-I-treated cells remained positive in a number of cells (Fig. 1A), indicating an arrest in the

Discussion

In this study, we demonstrated that apoA-I inhibits the differentiation from monocytes into DC in vitro, and also inhibits the ability of the mature DC to secrete IL-12 upon activation by CD40 and IFN-γ, while producing PGE2 and IL-10 during differentiation. Also, apoA-I inhibited immature DC functions, most notably, allogeneic T cell stimulation. ApoA-I-induced down-regulation of costimulatory molecules and MHC class II expression resulted in the inhibition of alloreactive T-cell activation

Acknowledgments

This work was supported by Grant, R11-2005-017-03001, of the Research Center for Women’s Diseases from the Korea Science and Engineering Foundation (KOSEF) and Grant, FG-3-1-04, of the 21C Frontier Functional Human Genome Project from the Ministry of Science and Technology (MOST), Korea.

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