期刊
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
卷 31, 期 3, 页码 499-508出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/08923970902814103
关键词
Zoledronic acid; dendritic cell; differentiation; maturation; interferon-gamma
资金
- Mackay Memorial Hospital [MMH-95108, MMH-9438]
- National Science Council, Taiwan [NSC 93-2413-H-195-001]
Zoledronic acid (ZOL), an effective nitrogen-containing bisphosphonate against excessive bone loss, has been shown affecting the function of cells of both innate and acquired immunity. In this study, we tested the effect of ZOL on differentiation and maturation of human myeloid dendritic cells (DC). When ZOL (1.1 to 10 mu M) was added to the culture of starting monocytes, but not to immature DC, the recovery rate of DC was markedly reduced in a concentration-dependent manner. The mature DC differentiated in the presence of ZOL had fewer and shorter cell projections. ZOL treatment affected DC differentiation and maturation in terms of lower expression of CID1a, CID11c, CD83, CD86, DC-SIGN, HLA-DR, and, in contrast, higher expression of CD80. IL-10 production by DC was inhibited by ZOL treatment whereas IL-12p70 secretion remained unchanged. Interestingly, ZOL augmented the allostimulatory activity of DC on naive CD4(++)CD45(++)RA(++)T cells in terms of their proliferation and interferon-gamma production. Addition of geranylgeraniol abrogated the effect of ZOL on DC differentiation and prenylation of Rap1A. It suggests that ZOL redirects DC differentiation toward a state of atypical maturation with allostimulatory function and this effect may go through prevention of Rap1A prenylation.
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