 |
JIFACTOR:Publisher: Peytchinski, Gospodin Iliev
ISSN: 1312 773X (Online)
Issue: 2014, vol. 20, issue 6
Subject Collection: Medicine
Pages: 542-546
DOI: 10.5272/jimab.2014206.542
Published online: 04 December 2014
J of IMAB 2014 Oct-Dec;20(6):542-546
ERK, p38 AND NF-kappaB SIGNALING IN MONOCYTE DERIVED DENDRITIC CELLS IN PATIENTS WITH MYELODYSPLASTIC SYNDROME.
Ilina Micheva1 
, Liana Gercheva1, Panos Ziros2, Nicholas Zoumbos2.
1) Hematology Division, Department of Internal Medicine, Medical University, Varna, Bulgaria
2) Hematology Division, Department of Internal Medicine, Patras University Medical School, Patras, Greece.
ABSTRACT:
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.
Key words: Myelodysplastic syndromes; dendritic cells; ERK, p38, NF-κB,
- Download FULL TEXT /PDF 1239 KB/
Please cite this article in PubMed Style or AMA (American Medical Association) Style:
Micheva I, Gercheva L, Ziros P, Zoumbos N. ERK, p38 and NF-kappaB signaling in monocyte derived dendritic cells in patients with myelodysplastic syndrome. J of IMAB. 2014 Oct-Dec;20(6):542-546. http://dx.doi.org/10.5272/jimab.2014206.542
Correspondence to: Dr. Ilina Micheva, Hematology Division, Department of Internal Medicine, Medical University; 1, Hristo Smirnenski str., 9010 Varna, Bulgaria; E-mail: ilinamicheva@gmail.com
REFERENCES:
1. Hart DN. Dendritic cells: Unique leukocyte populations which control the primary immune response. Blood. 1997 Nov 1;90(9):3245-87. [PubMed]
2. Castiello L, Sabatino M, Jin P, Clayberger C, Marincola FM, Krensky AM, et al. Monocyte-derived DC maturation strategies and related pathways: a transcriptional view. Cancer Immunol Immunother. 2011 Apr;60(4):457-66. [PubMed] [CrossRef]
3. Kerkhoff N, Bontkes HJ, Westers TM, de Gruijl TD, Kordasti S, van de Loosdrec AA. Dendritic cells in myelodysplastic syndromes: from pathogenesis to immunotherapy. Immunotherapy. 2013 Jun;5(6):621-37. [PubMed] [CrossRef]
4. Micheva I, Thanopoulou E, Michalopoulou S, Karakantza M, Kouraklis-Symeonidis A, Mouzaki A, et al. Defective tumor necrosis factor alpha-induced maturation of monocyte-derived dendritic cells in patients with myelodysplastic syndromes. Clin Immunology. 2004 Dec;113(3):310-7. [PubMed] [CrossRef]
5. Arrighi JF, Rebsamen M, Rousset F, Kindler V, Hauser C. A critical role for p38 mitogen-activated protein kinase in the maturation of human blood-derived dendritic cells induced by lipopolysaccharide, TNF-alpha, and contact sensitizers. J Immunol. 2001 Mar 15;166(6):3837-45. [PubMed] [CrossRef]
6. Ardeshna KM, Pizzey AR, Devereux S, Khwaja A. The PI3 kinase, p38 SAP kinase, and NF-kappaB signal transduction pathways are involved in the survival and maturation of lipopolysaccharide-stimulated human monocyte-derived dendritic cells. Blood. 2000 Aug 1;96(3):1039-46. [PubMed]
7. Pan K, Wang H, Liu WL, Zhang HK, Zhou J, Li JJ, et al. The pivotal role of p38 and NF-kappaB signal pathways in the maturation of human monocyte-derived dendritic cells stimulated by streptococcal agent OK-432. Immunobiology. 2009; 214(5):350-8. [PubMed] [CrossRef]
8. Puig-Kröger A, Relloso M, Fernández-Capetillo O, Zubiaga A, Silva A, Bernabéu C, et al. Extracellular signal-regulated protein kinase signaling pathway negatively regulates the phenotypic and functional maturation of monocyte-derived human dendritic cells. Blood. 2001 Oct 1;98(7):2175-82. [PubMed] [CrossRef]
9. Rescigno M, Martino M, Sutherland SL, Gold MR, Ricciardi-Castagnoli P. Dendritic cell survival and maturation are regulated by different signaling pathways. J Exp Med. 1998 Dec 7;188(11):2175-80. [PubMed]
10. O’Sullivan BJ, Thomas R. CD40 ligation conditions dendritic cell antigen-presenting function through sustained activation of NF-kappaB. J Immunol. 2002 Jun 1;168(11):5491-8. [PubMed]].
Received: 28 September 2014
Published online: 04 December 2014