<i>κ</i>-Carrageenan Enhances Lipopolysaccharide-Induced Interleukin-8 Secretion by Stimulating the Bcl10-NF-<i>κ</i>B Pathway in HT-29 Cells and Aggravates<i>C</i>.<i>freundii</i>-Induced Inflammation in Mice

Abstract

<i>Background.</i> The dietary usage of carrageenan as common food additive has increased observably over the last 50 years. But there is substantial controversy about its safety. <i>Methods.</i> We investigated whether the <i>κ</i>-carrageenan could enhance lipopolysaccharide-induced IL-8 expression by studying its actions on the TLR4-NF-<i>κ</i>B pathway. The aggravating effect of <i>κ</i>-carrageenan on <i>Citrobacter freundii</i> DBS100-induced intestinal inflammation was also investigated in a mouse model. <i>Results.</i> Our data show that <i>κ</i>-carrageenan pretreatment promoted LPS-induced IL-8 expression in HT-29 cells. Although CD14, MD-2, and TLR4 were upregulated, the binding of LPS was not enhanced. However, the pathway of Bcl10-NF-<i>κ</i>B was triggered. Interestingly, <i>κ</i>-carrageenan competitively blocked the binding of FITC-LPS. Furthermore, pretreatment with <i>κ</i>-carrageenan for one week previous to gavage with <i>C. freundii</i> DBS100 markedly aggravated weight loss, mortality, and colonic damage. The secretion of cytokines was unbalanced and the ratio of Tregs was decreased significantly. In addition, <i>κ</i>-carrageenan, together with <i>C. freundii</i> DBS100, enhanced the transcription and secretion of TLR4 and NF-<i>κ</i>B. <i>Conclusions</i>. <i>κ</i>-Carrageenan can synergistically activate LPS-induced inflammatory through the Bcl10-NF-<i>κ</i>B pathway, as indicated by its aggravation of <i>C. freundii</i> DBS100-induced colitis in mice. <i>General Significance.</i> Our results suggest that <i>κ</i>-carrageenan serves as a potential inflammatory agent that magnifies existing intestinal inflammation.