ERK, p38 AND NF-kappaB SIGNALING IN MONOCYTE DERIVED DENDRITIC CELLS IN PATIENTS WITH MYELODYSPLASTIC SYNDROME.
| Autor: | Ilina Micheva, Liana Gercheva, Panos Ziros, Nicholas Zoumbos |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | Journal of IMAB, Vol 20, Iss 6, Pp 542-546 (2014) |
| Druh dokumentu: | article |
| ISSN: | 1312-773X 70585962 |
| DOI: | 10.5272/jimab.2014206.542 |
| Popis: | We have previously demonstrated that in patients with myelodysplastic syndrome (MDS) monocyte-derived DCs (MoDC) exhibit some phenotypic and functional abnormalities. However, the mechanisms underlying the defective response have not yet been clarified. Aim: In the present study three different signaling pathways, ERK, p38K and NF-κB, were studied on MoDC from patients with MDS. Materials and methods: 7 patients with MDS and 5 healthy controls were included in the study. MACS separated CD14 cells were cultured for DC generation and further stimulated with TNF-α and LPS. A migration assay and ELISA were performed for the analysis of migration and IL-12p70 secretion. Western blot analysis was used for the detection of the phosphorylated forms of ERK and p38K. NF-κB binding activity was evaluated by electrophoretic mobility shift assay (EMSA). Results: In 6/7 patients the NF-κB binding activity in TNF-α and LPS stimulated MoDCs was lower compared to controls. This was accompanied by lower migratory capacity and IL-12p70 secretion. TNF-α and LPS induced phosphorylation of p38 and ERK at similar levels in control MoDC, whereas in MDS MoDC the pattern was heterogeneous with predominant activation of ERK over p38K. Conclusion: Our results provide strong evidence that defective signaling through NF-κB and MAPK underlies the functional abnormalities of MoDC in patients with MDS. |
| Databáze: | Directory of Open Access Journals |
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