The role of p38 mitogen-activated protein kinase in serum-induced leukemia inhibitory factor secretion by bone marrow stromal cells from pediatric myelodysplastic syndromes.
Stromal cells from pediatric myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) associated with MDS (MDS-AML) present high expression of leukemia inhibitor factor (LIF). We demonstrated using mitogen-activated protein kinase (MAPK) inhibitors that in stromal cells from pediatric MDS and MDS-AML, p38MAPK was critical in serum-induced secretion of LIF. The serum induction of phosphorylated p38MAPK form was observed only in stromal cells from healthy children, whereas in MDS and MDS-AML basal levels were maintained suggesting constitutive p38MAPK activation. Our study suggested the possible importance in pediatric MDS of p38MAPK signaling pathway which may be a future therapeutic target.
da Costa
Simone V
SV
Departamento de Radiologia, Universidade de São Paulo, São Paulo, Brazil.
Roela
Rosimeire A
RA
Junqueira
Mara Souza
MS
Arantes
Camila
C
Brentani
M Mitzi
MM
D000873:Anthracenes / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007223:Infant; D053605:Leukemia Inhibitory Factor / Q000378:metabolism*; D008297:Male; D009190:Myelodysplastic Syndromes / Q000378:metabolism* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D044967:Serum / Q000502:physiology; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
D000873:Anthracenes; D005419:Flavonoids; D007093:Imidazoles; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C432165:pyrazolanthrone; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one