期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 283, 期 16, 页码 10550-10558出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M708833200
关键词
-
资金
- NHLBI NIH HHS [R01 HL052622-05, R01 HL062244, R01 HL062244-05A1, R01 HL052622] Funding Source: Medline
- NIDDK NIH HHS [DK54016, P01 DK067887, R01 DK068324, DK68324, R01 DK054016] Funding Source: Medline
- NIGMS NIH HHS [R01 GM038060, R01 GM038060-19] Funding Source: Medline
The sulfated polysaccharide carrageenan (CGN) induces activation of NF kappa B and interleukin 8 (IL-8) in human colonic epithelial cells through a pathway of innate immunity mediated by Bcl10 (B-cell CLL/lymphoma 10). In this report, we identify Toll-like receptor 4 (TLR4), a member of the family of innate immune receptors, as the surface membrane receptor for CGN in human colonic epithelial cells. Experiments with fluorescence-tagged CGN demonstrated a marked reduction in binding of CGN to human intestinal epithelial cells and to RAW 264.7 mouse macrophages, following exposure to TLR4 blocking antibody (HTA-125). Binding of CGN to 10ScNCr/23 mouse macrophages, which are deficient in the genetic locus for TLR4, was absent. Additional experiments with TLR4 blocking antibody and TLR4 small interfering RNAs showed 80% reductions in CGN-induced increases in Bcl10 and IL-8. Transfection with dominant-negative MyD88 plasmid demonstrated MyD88 dependence of the CGN-TLR4-triggered increases in Bcl10 and IL-8. Therefore, these results indicate that CGN-induced inflammation in human colonocytes proceeds through a pathway of innate immunity, perhaps related to the unusual alpha-1,3-galactosidic linkage characteristic of CGN, and suggest how dietary CGN intake may contribute to human intestinal inflammation. Because CGN is a commonly used food additive in the Western diet, clarification of its effects and mechanisms of action are vital to issues of food safety.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据