One and two-level regulation patterns affecting NF-kappa B mRNA and nuclear NF-kappa B activity after treatment with TNF-alpha, IFN-gamma and IL-4.
The transactivating nuclear factor NF-kappa B is believed to be important in the pathophysiology of many cellular systems and mainly during HIV infection. kappa B activation has also been implicated in the process of differentiation as a cell progresses to a more mature and functional stage. As induction of differentiation equals growth retardation we undertook this study in order to establish the role of NF-kappa B in cell growth and maturity. Thus we employed the well described HL-60 cellular system that expresses constitutively basal amounts of NF-kappa B and is susceptible to NF-kappa B induction by various biological or chemical agents. We also used known inducers of differentiation like TNF-alpha, IFN-gamma and IL-4 that interact via their corresponding surface receptors found on HL-60 cells. We first studied by Northern analysis the possible correlation between c-myc and NF-kappa B precursor (p105) mRNA. We witnessed that all three cytokines were able to confer proliferative senescence and down-regulate concomitantly c-myc and NF-kappa B mRNA levels, events chronologically in accord with induction of differentiation as assessed by the induction of HLA-DR surface antigens. It is known that TNF-alpha is capable of inducing nuclear kappa B activity in HL-60 as the cells progress to a more mature stage. Therefore we examined whether the other two cytokines could do the same during the time they lead the cells to a differentiated phenotype. If this was the case, nuclear activation of NF-kappa B should be obtained by the same factors.(ABSTRACT TRUNCATED AT 250 WORDS)
Vassiliadis
S
S
Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.
Stravopodis
D
D
Kyrpides
N
N
Grigoriou
M
M
Papamatheakis
J
J
D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma