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.
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 theκ-carrageenan could enhance lipopolysaccharide-induced IL-8 expression by studying its actions on the TLR4-NF-κB pathway. The aggravating effect ofκ-carrageenan onCitrobacter freundiiDBS100-induced intestinal inflammation was also investigated in a mouse model.Results.Our data show thatκ-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 withκ-carrageenan for one week previous to gavage withC. freundiiDBS100 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 withC. freundiiDBS100, 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 ofC. freundiiDBS100-induced colitis in mice.General Significance.Our results suggest thatκ-carrageenan serves as a potential inflammatory agent that magnifies existing intestinal inflammation.
Key Laboratory of Applied Marine Biotechnology of Zhejiang Province, Ningbo University, Ningbo, Zhejiang 315211, China.
Wei
0000-0002-0858-8086
W
Wu
Key Laboratory of Applied Marine Biotechnology of Zhejiang Province, Ningbo University, Ningbo, Zhejiang 315211, China.
Zhanghe
Z
Zhen
Key Laboratory of Applied Marine Biotechnology of Zhejiang Province, Ningbo University, Ningbo, Zhejiang 315211, China.
Tingting
T
Niu
Key Laboratory of Applied Marine Biotechnology of Zhejiang Province, Ningbo University, Ningbo, Zhejiang 315211, China.
Xiaojuan
X
Zhu
Key Laboratory of Applied Marine Biotechnology of Zhejiang Province, Ningbo University, Ningbo, Zhejiang 315211, China.
Yuli
Y
Gao
Key Laboratory of Applied Marine Biotechnology of Zhejiang Province, Ningbo University, Ningbo, Zhejiang 315211, China.
Jiangyan
J
Yan
Key Laboratory of Applied Marine Biotechnology of Zhejiang Province, Ningbo University, Ningbo, Zhejiang 315211, China.
Yu
Y
Chen
Collaborative Innovation Center for Zhejiang Marine High-Efficiency and Healthy Aquaculture, Zhejiang 315211, China.
Xiaojun
0000-0003-0257-0157
X
Yan
Collaborative Innovation Center for Zhejiang Marine High-Efficiency and Healthy Aquaculture, Zhejiang 315211, China.
Haimin
0000-0002-1713-0026
H
Chen
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D000074018:B-Cell CLL-Lymphoma 10 Protein; D015153:Blotting, Western; D002351:Carrageenan / Q000494:pharmacology*; D016971:Citrobacter freundii / Q000276:immunology / Q000472:pathogenicity*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology* / Q000382:microbiology; D016209:Interleukin-8 / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D002351:Carrageenan