Unknown

Dataset Information

0

Autophagosomal IkappaB alpha degradation plays a role in the long term control of tumor necrosis factor-alpha-induced nuclear factor-kappaB (NF-kappaB) activity.


ABSTRACT: Transcription factor NF-?B is persistently activated in many chronic inflammatory diseases and cancers. The short term regulation of NF-?B is well understood, but little is known about the mechanisms of its long term activation. We studied the effect of a single application of TNF-? on NF-?B activity for up to 48 h in intestinal epithelial cells. Results show that NF-?B remained persistently activated up to 48 h after TNF-? and that the long term activation of NF-?B was accompanied by a biphasic degradation of I?B?. The first phase of I?B? degradation was proteasome-dependent, but the second was not. Further investigation showed that TNF-? stimulated formation of autophagosomes in intestinal epithelial cells and that I?B? co-localized with autophagosomal vesicles. Pharmacological or genetic blockade of autophagosome formation or the inhibition of lysosomal proteases decreased TNF-?-induced degradation of I?B? and lowered NF-?B target gene expression. Together, these findings indicate a role of autophagy in the control of long term NF-?B activity. Because abnormalities in autophagy have been linked to ineffective innate immunity, we propose that alterations in NF-?B may mediate this effect.

SUBMITTER: Colleran A 

PROVIDER: S-EPMC3123056 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Autophagosomal IkappaB alpha degradation plays a role in the long term control of tumor necrosis factor-alpha-induced nuclear factor-kappaB (NF-kappaB) activity.

Colleran Amy A   Ryan Aideen A   O'Gorman Angela A   Mureau Coralie C   Liptrot Catherine C   Dockery Peter P   Fearnhead Howard H   Egan Laurence J LJ  

The Journal of biological chemistry 20110331 26


Transcription factor NF-κB is persistently activated in many chronic inflammatory diseases and cancers. The short term regulation of NF-κB is well understood, but little is known about the mechanisms of its long term activation. We studied the effect of a single application of TNF-α on NF-κB activity for up to 48 h in intestinal epithelial cells. Results show that NF-κB remained persistently activated up to 48 h after TNF-α and that the long term activation of NF-κB was accompanied by a biphasic  ...[more]

Similar Datasets

| S-EPMC2660438 | biostudies-literature
| S-EPMC2900662 | biostudies-literature
| S-EPMC1831796 | biostudies-literature
| S-EPMC1221304 | biostudies-other
| S-EPMC2718698 | biostudies-literature
| S-EPMC2688722 | biostudies-literature
| S-EPMC3123049 | biostudies-literature
| S-EPMC1276939 | biostudies-literature
| S-EPMC2673708 | biostudies-literature
| S-EPMC356971 | biostudies-literature