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.
journal_name
Int J Colorectal Disjournal_title
International journal of colorectal diseaseauthors
Parhar K,Morse J,Salh Bdoi
10.1007/s00384-006-0193-7subject
Has Abstractpub_date
2007-06-01 00:00:00pages
601-9issue
6eissn
0179-1958issn
1432-1262journal_volume
22pub_type
杂志文章abstract：PURPOSE:Postoperative ileus (POI) is one of the complications that can occur after every surgical procedure including arthroplasty. It can have detrimental consequences for the patient and portrays an economic burden on health care systems. The risk factors for POI after arthroplasty described in the literature are sca...
journal_title：International journal of colorectal disease
pub_type： 杂志文章
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journal_title：International journal of colorectal disease
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journal_title：International journal of colorectal disease
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journal_title：International journal of colorectal disease
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