Zoledronic acid, an aminobisphosphonate, modulates differentiation and maturation of human dendritic cells.
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 microM) 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 CD1a, CD11c, 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.
Chen
Yu-Jen
YJ
Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan.
Chao
K S Clifford
KS
Yang
Yuh-Cheng
YC
Hsu
Ming-Ling
ML
Lin
Chin-Ping
CP
Chen
Yu-Yawn
YY
D056704:Adaptive Immunity / Q000187:drug effects / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004164:Diphosphonates / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D017368:Protein Prenylation / Q000187:drug effects / Q000276:immunology; D000077211:Zoledronic Acid; D020827:rap1 GTP-Binding Proteins / Q000276:immunology
D000943:Antigens, Differentiation; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; C430803:RAP1A protein, human; D018664:Interleukin-12; D000077211:Zoledronic Acid; D020827:rap1 GTP-Binding Proteins