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Prolongation of Carrageenan-induced Inflammation in Human Colonic Epithelial Cells by Activation of an NFκB – BCL10 Loop

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Title: Prolongation of Carrageenan-induced Inflammation in Human Colonic Epithelial Cells by Activation of an NFκB – BCL10 Loop
Author(s): Borthakur, Alip; Bhattacharyya, Sumit; Natarajan, Arivarasu A.; Kumar, Anoop; Dudeja, Pradeep K.; Tobacman, Joanne K.
Abstract: Carrageenan, a sulfated polysaccharide that is widely used as a food additive, induces inflammatory responses in animal models and human cells. The carrageenan-induced inflammatory cascades involve TLR4- and BCL10-dependent activation of NF-κB, leading to increased IL-8 production. Translocations involving BCL10 in the mucosa-associated lymphoid tissue (MALT) lymphomas are associated with constitutive activation of NF-κB. This report presents a mechanism by which carrageenan exposure leads to prolonged activation of both BCL10 and NF-κB in human colonic epithelial cells. Study findings demonstrate that nuclear RelA and RelB bind to an NF-κB binding motif in the BCL10 promoter in human colonic epithelial NCM460 and HT-29 cells. In vitro oligonucleotide binding assay, non-radioactive gel shift assay, and chromatin immunoprecipitation (ChIP) indicate binding of RelA and RelB to the BCL10 promoter. Prolonged inflammation follows activation of the BCL10-NFκB inflammatory loop in response to carrageenan, shown by increased BCL10, RelA, and IL-8 for 36 to 48 hours and increased RelB for 24 hours following withdrawal of carrageenan after 12 hours. In contrast, exposure to dextran sulfate sodium, which does not cause inflammation through TLR4 and BCL10 in the colonic epithelial cells, did not provoke prolonged activation of inflammation. The carrageenan-enhanced BCL10 promoter activity was blocked by caffeic acid phenethyl ester (CAPE) and MB-132 which inhibit NF-κB activation. These results indicate that NF-κB binding to the BCL10 promoter can lead to prolonged activation of the carrageenan-induced inflammatory cascade by a transcriptional mechanism involving an NF-κB – BCL10 loop.
Issue Date: 2012-08
Publisher: Elsevier
Citation Info: Borthakur, A., S. Bhattacharyya, et al. (2012). "Prolongation of carrageenan-induced inflammation in human colonic epithelial cells by activation of an NF kappa B-BCL10 loop." Biochimica et Biophysica Acta-Molecular Basis of Disease 1822(8): 1300-1307. DOI: 10.1016/j.bbadis.2012.05.001
Type: Article
Description: NOTICE: this is the author’s version of a work that was accepted for publication in Biochimica et Biophysica Acta-Molecular Basis of Disease. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Biochimica et Biophysica Acta-Molecular Basis of Disease, [Vol 1822, Issue 8, (August 2012)] DOI:10.1016/j.bbadis.2012.05.001
ISSN: 0925-4439
Sponsor: Supported by Department of Veterans Affairs and the NIDDK (R01-DK54016, R01-DK81858 and PO1-DK67887).
Date Available in INDIGO: 2012-09-10

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