文本框: INSULIN-LIKE GROWTH FACTOR 1 (IGF-1) CAN PROMOTE CORD BLOOD MONOCYTE-DERIVED DENDRITIC CELL MATURATION AND INHIBIT THEIR APOPTOSIS
Liu EM, Law HKW and Lau YL
Dept. of Paediatrics, The University of Hong Kong, Hong Kong, China

Objective: In order to further investigate the effects of IGF-1 on cord blood (CB) immune function, we studied the effects of IGF-1 on the maturation and survival of CB monocyte-derived dendritic cells (DCs).
Methods: CB CD14 positive monocytes were purified by immunomagnetic separation and cultured in RPMI-1640 medium supplemented with 10% FCS, IL-4 and GM-CSF for 5 days. The monocyte-derived DCs were then washed and resuspended in serum free, hormone free medium (DMEM-F12) with IL-4 + GM-CSF ± IGF-1 for further 2 days’ culture. Immunophenotype and cell apoptosis as assayed by annexin V and popidium iodide staining were analyzed by 3-color flow cytometry .
Results: Compared with IL-4 + GM-CSF stimulation alone, IGF-1 significantly increased CD83, CD86, CD40 and MHC class II expression level and down-regulated mannose receptor (MR) expression in CB monocyte-derived DCs. Furthermore, IGF-1 promoted the survival of CB monocyte-derived DCs and inhibited their apoptosis. These effects of IGF-1 could be fully blocked by PD98059, which is an inhibitor of the MEK pathway, whereas the addition of anti-TNFa could not neutralize the effects of IGF-1 on CB monocyte-derived DCs. 
Conclusions: IGF-1 promotes CB monocyte-derived DCs maturation and survival via MEK pathway and not through the effect of TNFa which is induced by IGF-1. These results suggest that the role of IGF-1 in potentiating immune response in neonates, including the role as neonatal vaccine adjuvant, should be further investigated.
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