NF-kappaB activation induced by Notch ligand stimulation in acute myeloid leukemia cells.
There are conflicting reports regarding the effects of Notch activation on nuclear factor-kappaB (NF-kappaB) activity. The relationships are cell type-dependent and have not been fully elucidated. We examined the effects of Notch activation induced by a recombinant Notch ligand, Delta-like1 (Dll1), on the NF-kappaB activity in two acute myeloid leukemia (AML) cell lines. We found that Delta1-induced Notch activation activated the NF-kappaB pathway in THP-1 cells. Regarding the possible mechanisms, Dll1 stimulation increased the mRNA and protein expression levels of some components of the NF-kappaB pathway and induced phosphorylation of IKKalpha/beta, IkappaB and RelA proteins after 24 or 48 h of stimulation. Since the phosphorylation required a long time, it did not appear to be caused by physical interactions between Notch and NF-kappaB proteins, but rather by indirect effects. One possible mechanism for the indirect effects was the observed induction of IL-1beta expression by Dll1 stimulation. On the other hand, Notch activation did not affect NF-kappaB activity in TMD7 cells. RelA was phosphorylated without stimulation, indicating that NF-kappaB was constitutively activated in TMD7 cells. To the best of our knowledge, this is the first study to investigate AML cells and use a recombinant Notch ligand to activate Notch. The present findings lead to better understanding of Notch functions, which have not been fully elucidated.
Itoh
Mai
M
Department of Laboratory Medicine, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Fu
Lu
L
Tohda
Shuji
S
D002135:Calcium-Binding Proteins; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D008565:Membrane Proteins / Q000494:pharmacology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051880:Receptors, Notch / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology
D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D051880:Receptors, Notch; D011994:Recombinant Proteins; D004247:DNA