Prolongation of carrageenan-induced inflammation in human colonic epithelial cells by activation of an NF魏B鈥怋CL10 loop

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• 作者：Alip Borthakur¹ ; Sumit Bhattacharyya¹ ; Arivarasu N. Anbazhagan ; Anoop Kumar ; Pradeep K. Dudeja ; Joanne K. Tobacman ; ^jkt@uic.edu
• 关键词：BCL10 ; B-cell leukemia/lymphoma 10 ; CAPE ; caffeic phenethyl ester ; CARMA ; caspase recruitment domain membrane-associated guanylate kinase ; CBM ; CARMA-BCL10-MALT complex ; CGN ; carrageenan ; ChIP ; chromatic immunoprecipitation ; DSS ; dextran sulfate sodium ; H
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Basis of Disease
• 出版年：2012
• 期刊代码：19_09254439
• 类别：bio
• 出版时间：August, 2012
• 卷：1822
• 期：8
• 页码：1300-1307
• 文件大小：747 K

摘要

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 toll-like receptor (TLR)4- and B-cell leukemia/lymphoma (BCL)10-dependent activation of NF-魏B, leading to increased IL-8 production. Translocations involving BCL10 in the mucosa-associated lymphoid tissue (MALT) lymphomas are associated with constitutive activation of NF-魏B. This report presents a mechanism by which carrageenan exposure leads to prolonged activation of both BCL10 and NF-魏B in human colonic epithelial cells. Study findings demonstrate that nuclear RelA and RelB bind to an NF-魏B 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-NF魏B inflammatory loop in response to carrageenan, shown by increased BCL10, RelA, and IL-8 for 36 to 48 h and increased RelB for 24 h following withdrawal of carrageenan after 12 h. 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-魏B activation. These results indicate that NF-魏B binding to the BCL10 promoter can lead to prolonged activation of the carrageenan-induced inflammatory cascade by a transcriptional mechanism involving an NF-魏B鈥怋CL10 loop.