Arsenite inhibits interleukin-6 production in human intestinal epithelial cells by down-regulating nuclear factor-κB activity

2002 ◽  
Vol 103 (4) ◽  
pp. 381-390 ◽  
Author(s):  
Dan D. HERSHKO ◽  
Bruce W. ROBB ◽  
Eric S. HUNGNESS ◽  
Guangju LUO ◽  
Xialing GUO ◽  
...  
Keyword(s):  
Dna Binding ◽  
Interleukin 6 ◽  
Sodium Arsenite ◽  
Nuclear Factor Κb ◽  
Inhibitory Effect ◽  
Binding Activity ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
Mobility Shift ◽  
Dna Binding Activity

Previous studies have suggested that the production of interleukin-6 (IL-6) is increased in the intestinal mucosa during inflammation, and that nuclear factor-κB (NF-κB) is an important regulator of the IL-6 gene in the enterocyte. We tested the hypothesis that sodium arsenite inhibits IL-6 production in stimulated enterocytes and that this effect of arsenite is caused by down-regulation of NF-κB activity. Cultured Caco-2 cells were treated with sodium arsenite and were then stimulated with IL-1β. IL-6 production and gene expression were determined by ELISA and reverse transcriptase–PCR respectively. NF-κB DNA binding activity was determined by electrophoretic mobility shift assay. IL-1β increased NF-κB DNA binding activity, IL-6 mRNA levels and IL-6 production. These effects of IL-1β were inhibited by treatment of the cells with sodium arsenite in a dose- and time-dependent fashion. When cells were transfected with a plasmid expressing the p65 subunit of NF-κB, the inhibitory effect of sodium arsenite on NF-κB activity and IL-6 production was blunted. These results suggest that sodium arsenite inhibits IL-6 production in enterocytes subjected to an inflammatory stimulus, and that this effect, at least in part, reflects down-regulated NF-κB activity.

UV stimulation induces nuclear factor κB (NF-κB) DNA-binding activity but not transcriptional activation

2001 ◽  
Vol 29 (6) ◽  
pp. 688-691 ◽  
Author(s):  
K. J. Campbell ◽  
N. R. Chapman ◽  
N. D. Perkins
Keyword(s):  
Dna Binding ◽  
Transcriptional Activation ◽  
Cellular Response ◽  
Uv Light ◽  
Binding Protein ◽  
Nuclear Factor Κb ◽  
Camp Response Element Binding ◽  
Binding Activity ◽  
Nuclear Factor ◽  
Dna Binding Activity

The cellular response to DNA-damaging agents is partly mediated by DNA-binding transcription factors such as p53 and nuclear factor κB (NF-κB). Typically NF-κB activation is associated with resistance to apoptosis. Following stimulation with UV light however, NF-κB activation has been shown to be required for programmed cell death. To study this effect further and to determine the relationship between NF-κB and p53 function, we have examined the effect of UV light on U2OS cells. UV stimulation resulted in the activation of NF-κB DNA-binding and the induction of p53. Surprisingly, and in contrast with tumour necrosis factor α stimulation, this UV-induced NF-κB was transcriptionally inert. These observations suggest a model in which the NF-κB switch from an anti-apoptotic to a pro-apoptotic role within the cell results from modulation of its ability to stimulate gene expression, possibly as a result of the ability of p53 to sequester transcriptional co-activator proteins such as p300/CREB (cAMP-response-element-binding protein)-binding protein.

scholarly journals UV-A-induced decrease in nuclear factor-κB activity in human keratinocytes

1999 ◽  
Vol 338 (3) ◽  
pp. 607-613 ◽  
Author(s):  
Mojgan DJAVAHERI-MERGNY ◽  
Marie-Pierre GRAS ◽  
Jean-Louis MERGNY ◽  
Louis DUBERTRET
Keyword(s):  
Gene Expression ◽  
Dna Binding ◽  
Uv Radiation ◽  
Human Keratinocytes ◽  
Nuclear Factor Κb ◽  
Binding Activity ◽  
Luciferase Reporter ◽  
Nuclear Factor ◽  
Protein Subunits ◽  
Dna Binding Activity

Previous reports have demonstrated an increase in nuclear factor-κB (NF-κB) activity in response to UV radiation. These studies have essentially focused on the DNA-damaging fraction of solar UV radiation (UV-B and UV-C). In contrast, the effects of UV-A radiation (320–400 nm) on NF-κB are not well known. In this study, we present evidence that UV-A radiation induces a marked decrease in NF-κB DNA-binding activity in NCTC 2544 human keratinocytes. In addition, NCTC 2544 keratinocytes pretreated with UV-A fail to respond to NF-κB inducers. Moreover, UV-A radiation induces a decrease in NF-κB-driven luciferase reporter gene expression in NCTC 2544 keratinocytes. The expression of the gene encoding IκBα (IκB is the NF-κB inhibitor), which is closely associated with NF-κB activity, is also reduced (3-fold) upon UV-A treatment. Our results indicate that the UV-A-induced decrease in NF-κB DNA-binding activity is associated with a decrease in the levels of the p50 and p65 protein subunits. This is the first evidence that an oxidative stress, such as UV-A radiation, may induce a specific decrease in NF-κB activity in mammalian cells, probably through degradation of NF-κB protein subunits. These findings suggest that UV-A could modulate the NF-κB-dependent gene expression.

scholarly journals Erythromycin Inhibits Transcriptional Activation of NF-κB, but not NFAT, through Calcineurin-Independent Signaling in T Cells

1999 ◽  
Vol 43 (11) ◽  
pp. 2678-2684 ◽  
Author(s):  
Yosuke Aoki ◽  
Peter N. Kao
Keyword(s):  
T Cells ◽  
Dna Binding ◽  
Transcriptional Activation ◽  
Calcium Ionophore ◽  
Inhibitory Effect ◽  
Binding Activity ◽  
Cytokine Gene Expression ◽  
Nuclear Factor ◽  
Mobility Shift ◽  
Activated T Cells

ABSTRACT The molecular mechanism of the anti-inflammatory effect of erythromycin (EM) was investigated at the level of transcriptional regulation of cytokine gene expression in T cells. EM (>10−6 M) significantly inhibited interleukin-8 (IL-8) expression but not IL-2 expression from T cells induced with 20 ng of phorbol 12-myristate 13-acetate (PMA) per ml plus 2 μM calcium ionophore (P-I). In electrophoretic mobility shift assays EM at 10−7 to 10−5 M concentrations inhibited nuclear factor kappa B (NF-κB) DNA-binding activities induced by P-I. Reporter gene assays also showed that EM (10−5 M) inhibited IL-8 NF-κB transcription by 37%. The inhibitory effects of EM on transcriptional activation of IL-2 and DNA-binding activity of nuclear factor of activated T cells (NFAT) were not seen in T cells. On the other hand, FK506, which is also a macrolide derivative, inhibited transcriptional activation of both NF-κB and NFAT more strongly than EM did. The mechanism of EM inhibition of transactivation of NF-κB was further investigated in transiently transfected T cells that express calcineurin A and B subunits. Expression of calcineurin did not render transactivation of NF-κB in T cells more resistant to EM, while the inhibitory effect of FK506 on transactivation of NF-κB was attenuated. These findings indicate that EM is capable of inhibiting expression of the IL-8 gene in T cells through transcriptional inhibition and that this inhibition is mediated through a non-calcineurin-dependent signaling event in T lymphocytes.

Decreased nuclear factor-κB DNA binding activity following permanent focal cerebral ischaemia in the rat

2000 ◽  
Vol 288 (1) ◽  
pp. 45-48 ◽  
Author(s):  
E.A Irving ◽  
S.J Hadingham ◽  
J Roberts ◽  
M Gibbons ◽  
M Chabot-Fletcher ◽  
...  
Keyword(s):  
Dna Binding ◽  
Cerebral Ischaemia ◽  
Nuclear Factor Κb ◽  
Binding Activity ◽  
Nuclear Factor ◽  
Focal Cerebral Ischaemia ◽  
Dna Binding Activity
Sign in / Sign up

Export Citation Format

Share Document