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Int J Colorectal Dis. 2007 Jun;22(6):601-9. Epub 2006 Sep 29.

The role of protein kinase CK2 in intestinal epithelial cell inflammatory signaling.

Author information

1
The Jack Bell Research Center, 2660 Oak Street, V6H 3Z6, Vancouver, British Columbia, Canada.

Abstract

BACKGROUND:

The transcription factor NF-kappaB is believed to play a key pathophysiological role in chronic intestinal inflammation. Further characterization of its mechanism of regulation, predominantly through cell signaling pathways, may provide clues as to the means of its intervention. One such potential signaling candidate is the protein kinase CK2. Despite its known ability to influence NF-kappaB activation, it has received no attention in this particular setting.

AIM:

To characterize the aspects of its activation in response to IL-1beta in the colonic cell lines Caco2 and HCT116.

MATERIALS AND METHODS:

A biochemical analysis of kinase activation was performed using phospho-specific antibodies as well as immune complex kinase assays; transcription factor activity was measured by transient transfection and luciferase-based NF-kappaB reporter assays; pro-inflammatory molecule expression was determined using RT-PCR.

RESULTS:

In this report, we show an enhanced activation of CK2 bound to IKKgamma or the p65 subunit of the NF-kappaB in response to IL-1beta stimulation of intestinal epithelial cells. Using two established NF-kappaB reporters, we demonstrate that CK2 is involved in NF-kappaB regulation through the p65 serine 529 site. Using co-immunoprecipitation studies, we also show that p65 is bound to CK2 predominantly in the nucleus. From a functional perspective, two CK2 specific inhibitors were then shown to attenuate IL-8 reporter activation. Finally, the expression of a series of pro-inflammatory molecules including IL-8, GRO-alpha, MCP-1, TNFalpha and iNOS were variably affected in response to CK2 inhibition.

CONCLUSION:

CK2 plays an active role in NF-kappaB signaling in intestinal epithelial cell lines and may represent a possible target for intervention.

PMID:
17009010
DOI:
10.1007/s00384-006-0193-7
[Indexed for MEDLINE]

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