期刊
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
卷 1780, 期 7-8, 页码 973-982出版社
ELSEVIER
DOI: 10.1016/j.bbagen.2008.03.019
关键词
carrageenan; reactive oxygen species (ROS); Bcl10 (B-cell CLL/lymphoma 10); Hsp27; MAPK; NF kappa B; IL-8; colonic epithelial cells; sulfate assimilation pathway
资金
- NIDDK NIH HHS [DK68324, P01 DK067887, R01 DK054016, R01 DK068324, DK54016] Funding Source: Medline
Carrageenans are highly sulfated polysaccharides that are widely used as food additives due to their ability to improve food texture. They are also widely recognized for their ability to induce inflammation in animal models of colitis. Recently, we reported that carrageenan (CGN) activated a pathway of innate immunity in human colonic epithelial cells mediated by Bcl10 (B-cell CLL/lymphoma 10). However, increases in phospho-I kappa B alpha and Interleukin-8 (IL-8) were not completely inhibited by silencing Bcl10, suggesting that CGN also influenced another mechanism, or mechanisms, of inflammation. In this report, we demonstrate that CGN increases production of reactive oxygen species (ROS) in human colonic epithelial cells. The combination of ROS quenching by the free radical scavenger Tempol and of Bcl10 silencing by siRNA completely inhibited the CGN-induced increases in nuclear NF kappa B (p65), phospho-I kappa B alpha, and secretion of IL-8. The CGN-induced increase in ROS was associated with declines in phosphorylation of MAPK 12 (p38 gamma), MAPK 13 (p38 delta), and heat-shock protein (Hsp) 27. The CGN-induced decline in phospho-Hsp27 was reversed by co-administration of Tempol (100 nM), but unaffected by silencing Bcl10. Since Hsp27 phosphorylation is inversely associated with phosphorylation of the I kappa B alpha kinase (IKK) signalosome, CGN exposure appears to affect the IKK signalosome by both the catalytic component, mediated by ROS-phospho-Hsp27, and the regulatory component, mediated by Bcl10 interaction with IKK gamma (Nemo). Hence, the CGN-activated inflammatory cascades related to innate immunity and to generation of ROS may be integrated at the level of the IKK signalosome. (C) 2008 Elsevier B.V. All rights reserved.
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