Dehydroxymethylepoxyquinomicin, a novel nuclear factor-κB inhibitor, prevents inflammatory injury induced by interferon-γ and histamine in NCTC 2544 keratinocytes

2010 ◽  
Vol 37 (7) ◽  
pp. 679-683 ◽  
Author(s):  
Venera Cardile ◽  
Massimo Libra ◽  
Silvia Caggia ◽  
Giuseppina Frasca ◽  
Kazuo Umezawa ◽  
...  
Keyword(s):  
Nuclear Factor Κb ◽  
Interferon Γ ◽  
Nuclear Factor ◽  
Inflammatory Injury

scholarly journals Small Molecule Inhibitors Targeting Nuclear Factor κB Activation Markedly Reduce Expression of Interleukin-2, but Not Interferon-γ, Induced by Phorbol Esters and Calcium Ionophores

2021 ◽  
Vol 22 (23) ◽  
pp. 13098
Author(s):  
Yumiko Tanaka ◽  
Ayaka Nakao ◽  
Yasunobu Miyake ◽  
Yukina Higashi ◽  
Riho Tanigaki ◽  
...  
Keyword(s):  
T Cells ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Nuclear Factor Κb ◽  
Interferon Γ ◽  
Effector T Cells ◽  
Nuclear Factor ◽  
Ifn Γ ◽  
Primary Effector ◽  
Mouse Lymphoma

The T-box transcription factor Eomesodermin (Eomes) promotes the expression of interferon-γ (IFN-γ). We recently reported that the small molecule inhibitors, TPCA-1 and IKK-16, which target nuclear factor κB (NF-κB) activation, moderately reduced Eomes-dependent IFN-γ expression in mouse lymphoma BW5147 cells stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin (IM). In the present study, we investigated the direct effects of NF-κB on IFN-γ expression in mouse lymphoma EL4 cells and primary effector T cells. Eomes strongly promoted IFN-γ expression and the binding of RelA and NFATc2 to the IFN-γ promoter when EL4 cells were stimulated with PMA and IM. Neither TPCA-1 nor IKK-16 reduced IFN-γ expression; however, they markedly decreased interleukin (IL)-2 expression in Eomes-transfected EL4 cells. Moreover, TPCA-1 markedly inhibited the binding of RelA, but not that of Eomes or NFATc2 to the IFN-γ promoter. In effector CD4+ and CD8+ T cells activated with anti-CD3 and anti-CD28 antibodies, IFN-γ expression induced by PMA and A23187 was not markedly decreased by TPCA-1 or IKK-16 under conditions where IL-2 expression was markedly reduced. Therefore, the present results revealed that NF-κB is dispensable for IFN-γ expression induced by PMA and calcium ionophores in EL4 cells expressing Eomes and primary effector T cells.

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