Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1038/s41467-018-04069-z |
Macrophage-derived IL-1 beta/NF-kappa B signaling mediates parenteral nutrition-associated cholestasis | |
El Kasmi, Karim C.1; 39;Alessandro, Angelo2 | |
2018-04-11 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Belgium; Germany |
英文摘要 | In infants intolerant of enteral feeding because of intestinal disease, parenteral nutrition may be associated with cholestasis, which can progress to end-stage liver disease. Here we show the function of hepatic macrophages and phytosterols in parenteral nutrition-associated cholestasis (PNAC) pathogenesis using a mouse model that recapitulates the human pathophysiology and combines intestinal injury with parenteral nutrition. We combine genetic, molecular, and pharmacological approaches to identify an essential function of hepatic macrophages and IL-1 beta in PNAC. Pharmacological antagonism of IL-1 signaling or genetic deficiency in CCR2, caspase-1 and caspase-11, or IL-1 receptor (which binds both IL-1 alpha and IL-1 beta) prevents PNAC in mice. IL-1 beta increases hepatocyte NF-kappa B signaling, which interferes with farnesoid X receptor and liver X receptor bonding to respective promoters of canalicular bile and sterol transporter genes (Abcc2, Abcb11, and Abcg5/8), resulting in transcriptional suppression and subsequent cholestasis. Thus, hepatic macrophages, IL-1 beta, or NF-kappa B may be targets for restoring bile and sterol transport to treat PNAC. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000429689800016 |
WOS关键词 | SALT EXPORT PUMP ; BILIARY CHOLESTEROL SECRETION ; SHORT-BOWEL SYNDROME ; LIVER-DISEASE ; INTESTINAL FAILURE ; LIPID EMULSIONS ; INTRAHEPATIC CHOLESTASIS ; ACID RECEPTOR ; PLANT STEROLS ; CHILDREN |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203786 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Colorado, Sect Pediat Gastroenterol Hepatol & Nutr, Dept Pediat, Sch Med, Aurora, CO 80045 USA; 2.Childrens Hosp Colorado, Digest Hlth Inst, Pediat Liver Ctr, Aurora, CO 80045 USA; 3.Catholic Univ Louvain, Lab Gastroenterol & Hepatol, GAEN, IREC, 1 Pl Univ, B-1348 Louvain La Neuve, Belgium; 4.Univ Colorado, Sch Med, Dept Pediat, Cardiovasc Pulm Res, 12800 East 19th Ave, Aurora, CO 80045 USA; 5.Univ Colorado, Sch Med, Dept Pediat, Div Pediat Crit Care, 12800 East 19th Ave, Aurora, CO 80045 USA; 6.Univ Colorado, Sch Med, Dept Pediat, Sect Neonatol, 12800 East 19th Ave, Aurora, CO 80045 USA; 7.Univ Colorado, Dept Pathol, Sch Med, Bldg RC-1,North Tower,12800 East 19th Ave, Aurora, CO 80045 USA; 8.Univ Colorado, Dept Biochem & Mol Genet, Sch Med, 12801,E 17th Ave, Aurora, CO 80045 USA; 9.Boehringer Ingelheim Pharma GmbH & Co KG, Dept Immunol & Resp, Birkendorferstr 65, D-88397 Biberach, Germany; 10.Univ Washington, Dept Pediat, Providence Pediat Gastroenterol, Anchorage, AK 99515 USA |
推荐引用方式 GB/T 7714 | El Kasmi, Karim C.,39;Alessandro, Angelo. Macrophage-derived IL-1 beta/NF-kappa B signaling mediates parenteral nutrition-associated cholestasis[J]. NATURE COMMUNICATIONS,2018,9. |
APA | El Kasmi, Karim C.,&39;Alessandro, Angelo.(2018).Macrophage-derived IL-1 beta/NF-kappa B signaling mediates parenteral nutrition-associated cholestasis.NATURE COMMUNICATIONS,9. |
MLA | El Kasmi, Karim C.,et al."Macrophage-derived IL-1 beta/NF-kappa B signaling mediates parenteral nutrition-associated cholestasis".NATURE COMMUNICATIONS 9(2018). |
条目包含的文件 | 条目无相关文件。 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论