κ-Carrageenan Enhances Lipopolysaccharide-Induced Interleukin-8 Secretion by Stimulating the Bcl10-NF-κB Pathway in HT-29 Cells and AggravatesC.freundii-Induced Inflammation in Mice

Abstract

Background. 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. Methods. We investigated whether the κ-carrageenan could enhance lipopolysaccharide-induced IL-8 expression by studying its actions on the TLR4-NF-κB pathway. The aggravating effect of κ-carrageenan on Citrobacter freundii DBS100-induced intestinal inflammation was also investigated in a mouse model. Results. Our data show that κ-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-κB was triggered. Interestingly, κ-carrageenan competitively blocked the binding of FITC-LPS. Furthermore, pretreatment with κ-carrageenan for one week previous to gavage with C. freundii 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, κ-carrageenan, together with C. freundii DBS100, enhanced the transcription and secretion of TLR4 and NF-κB. Conclusions. κ-Carrageenan can synergistically activate LPS-induced inflammatory through the Bcl10-NF-κB pathway, as indicated by its aggravation of C. freundii DBS100-induced colitis in mice. General Significance. Our results suggest that κ-carrageenan serves as a potential inflammatory agent that magnifies existing intestinal inflammation.

Dietary κ-carrageenan facilitates gut microbiota-mediated intestinal inflammation

“…These are consistent with most o cial reports [1,3,4]. However, in the present study, 90 days of κ-CGN gavage promoted colitis-associated gut in ammatory symptoms in C. rodentium-treated mice, which also had been observed in our short-term tests [11]. We therefore hypothesized that κ-CGN provides a favorable environment for in ammation.…”

“…Mice were treated with different concentrations of κ-CGN (1.7 mg/kg, CGN-L; 8.3 mg/kg, CGN-M; or 41.7 mg/kg, CGN-H; n = 32) for 90 days [9][10][11]. For the treatment, 8 mice were treated with κ-CGN only; 8 mice with κ-CGN and C. rodentium (CGN C. rodentium , gavaged daily with 10 9 CFU/mouse of C. rodentium for 3 consecutive days); 8 with κ-CGN and probiotics (CGN Pro+ , gavaged with 10 9 CFU/mouse suspension of 2 probiotics for 23 days); and 8 with κ-CGN, C. rodentium and probiotic (CGN C. rodentium+Pro+ , treated with 2 probiotics for 23 days, stopped treatment for a week, followed by gavage with C. rodentium for 3 days).…”

“…These con icting ndings appear to stem from scienti cally rigorous experiments, which suggests that the in ammatory potential of CGN could be conditional. We previously showed that a short course (1-2 weeks) of pre-treatment of mice with CGN led to increased in ammatory bowel symptoms caused by oxazolone, trinitrobenzene sulfonic acid and Citrobacter rodentium [9][10][11].…”

Growth hormone‐releasing hormone antagonists reduce prostatic enlargement and inflammation in carrageenan‐induced chronic prostatitis

“…Carrageenan‐induced mouse paw oedema is used extensively to study general anti‐inflammatory actions of new compounds . Its molecular mechanism in epithelial cells was mainly characterized in the intestine; carrageenan binds and activates toll‐like receptor 4 (TLR4) and stimulates BCL‐10 and NFκB activation leading to increased IL‐8 expression . In carrageenan‐induced prostatitis, the NALP1 inflammasome pathway is activated leading to an elevated level of IL‐1β and activation of caspase 1 .…”

“…42 Its molecular mechanism in epithelial cells was mainly characterized in the intestine; carrageenan binds and activates tolllike receptor 4 (TLR4) and stimulates BCL-10 and NFκB activation leading to increased IL-8 expression. [43][44][45] In carrageenan-induced prostatitis, the NALP1 inflammasome pathway is activated leading to an elevated level of IL-1β and activation of caspase 1. 46 Normal prostates express TLR4 receptors 47 providing further evidence on the anti-inflammatory actions of GHRH antagonists as previously reported by us in autoimmune prostatic inflammation 21 and in testosterone-induced BPH.…”