综述 REVIEW

脂多糖诱导的肠屏障蛋白及其信号通路研究进展

  • 王梦竹 ,
  • 贾军峰 ,
  • 崔一喆 ,
  • 王秋菊
展开
  • 1. 黑龙江八一农垦大学动物科技学院, 大庆 163319;
    2. 广东省农业科学院动物科学研究所, 农业部华南动物营养与饲料重点实验室, 广州 510640
王梦竹(1994-),女,贵州贵阳人,硕士研究生,从事畜禽肠道营养健康研究。E-mail:wangmengzhu06@163.com

收稿日期: 2019-10-31

  网络出版日期: 2020-05-15

基金资助

黑龙江八一农垦大学研究生科研创新资助项目(YJSCX2018-Y35);中国博士后科学基金会(第62批面上一等资助)(2017M620124);中国博士后科学基金会(第十一批中国博士后科学基金特别资助)(2018T110320)

Research Progress on Lipopolysaccharide-Induced Intestinal Barrier Signaling Pathway

  • WANG Mengzhu ,
  • JIA Junfeng ,
  • CUI Yizhe ,
  • WANG Qiuju
Expand
  • 1. College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China;
    2. Key Laboratory of Animal Nutrition and Feed Science in South China of Ministry of Agriculture, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China

Received date: 2019-10-31

  Online published: 2020-05-15

摘要

脂多糖(LPS)是诱导肠黏膜损伤的应激源之一,其不仅可损伤肠道,还会引发细菌移位,损伤的胃肠道屏障会造成肠道紧密连接蛋白异常表达,使得内毒素、病原体等得以穿过肠壁,诱导活化细胞表面Toll样受体4(TLR4)激发下游的核因子-κB(NF-κB)信号通路,并合成释放细胞炎性因子,继而加重肠道的损伤。本文就LPS在诱导炎症反应发生的作用以及其潜在作用作一综述。

关键词: LPS; TLR4; 紧密连接蛋白; NF-κB

本文引用格式

王梦竹 , 贾军峰 , 崔一喆 , 王秋菊 . 脂多糖诱导的肠屏障蛋白及其信号通路研究进展[J]. 动物营养学报, 2020 , 32(5) : 2060 -2065 . DOI: 10.3969/j.issn.1006-267x.2020.05.014

Abstract

Lipopolysaccharide(LPS)is a stressor that induces intestinal mucosal damage. It not only damages the intestine but also causes bacterial translocation. The damaged gastrointestinal barrier causes abnormal expression of tight junction proteins in the intestine, allowing endotoxin and pathogens to pass through. LPS induces the activation of nuclear factor-κB (NF-κB) signaling pathway through the Toll-like 4 receptor (TLR4) on cellular surface, then releases proinflammatory cytokine which aggravates the damage of intestine. This paper focus on the role of LPS in the processing of inflammation induction and its underlying pathways.

参考文献

[1] FAWLEY J,KOEHLER S,CABRERA S,et al.Intestinal alkaline phosphatase deficiency leads to dysbiosis and bacterial translocation in the newborn intestine[J].Journal of Surgical Research,2017,218:35-42.
[2] REITZ M,OGER P,MEYER A,et al.Importance of the O-antigen,core-region and lipid A of rhizobial lipopolysaccharides for the induction of systemic resistance in potato to Globodera pallida[J].Nematology,2002,4(1):73-79.  
[3] SCHROMM A B,BRANDENBURG K,LOPPNOW H,et al.Biological activities of lipopolysaccharides are determined by the shape of their lipid A portion[J].The FEBS Journal,2000,267(7):2008-2013.
[4] TANG W H W,WANG Z N,LEVISON B S,et al.Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk[J].The New England Journal of Medicine,2013,368(17):1575-1584.  
[5] PARK B S,LEE J O.Recognition of lipopolysaccharide pattern by TLR4 complexes[J].Experimental & Molecular Medicine,2013,45(12):e66.
[6] CASELLA C R,MITCHELL T C.Putting endotoxin to work for us:monophosphoryl lipid A as a safe and effective vaccine adjuvant[J].Cellular and Molecular Life Sciences,2008,65(20):3231-3240.  
[7] MATA-HARO V,CEKIC C,MARTIN M,et al.The vaccine adjuvant monophosphoryl lipid A as a TRIF-biased agonist of TLR4[J].Science,2007,316(5831):1628-1632.  
[8] 贾军峰,王梦竹,崔一喆,等.脂多糖致炎时间对小鼠血液免疫与肠道组织形态的影响[J].动物营养学报,2018,30(9):3609-3616.
[9] 李先根,涂治骁,王树辉,等.亚麻籽油对脂多糖刺激断奶仔猪肠黏膜结构和免疫细胞的影响[J].动物营养学报,2018,30(2):515-523.
[10] 杨侃侃,边连全,刘显军,等.刺五加多糖对断奶仔猪生长性能、部分血液生化指标及抗氧化能力的影响[J].饲料研究,2013(3):14-17.
[11] TILG H,ZMORA N,ADOLPH T E,et al.The intestinal microbiota fuelling metabolic inflammation[J].Nature Reviews Immunology,2019:1-15,doi:10.1038/s41577-019-0198-4.
[12] DOKLADNY K,ZUHL M N,MOSELEY P L.Intestinal epithelial barrier function and tight junction proteins with heat and exercise[J].Journal of Applied Physiology,2016,120(6):692-701.  
[13] 崔巍,闻颖,董亚珞,等.谷氨酰胺对体外培养肠上皮细胞屏障通透性的影响[J].世界华人消化杂志,2008,16(33):3729-3733.
[14] WU H,LUO T,LI Y M,et al.Granny Smith apple procyanidin extract upregulates tight junction protein expression and modulates oxidative stress and inflammation in lipopolysaccharide-induced Caco-2 cells[J].Food & Function,2018,9(6):3321-3329.  
[15] 陈晓明.MSC及Poly(I:C)预刺激后对脓毒症大鼠肠屏障功能的保护作用及机制[D].硕士学位论文.重庆:第三军医大学,2016.
[16] YANG F J,WANG A N,ZENG X F,et al.Lactobacillus reuteri I5007 modulates tight junction protein expression in IPEC-J2 cells with LPS stimulation and in newborn piglets under normal conditions[J].BMC Microbiology,2015,15(1):32.
[17] 刘畅.探究TLR4对小鼠肠黏膜紧密连接蛋白的调控作用[D].硕士学位论文.沈阳:中国医科大学,2018.
[18] HE C M,DENG J,HU X,et al.Vitamin a inhibits the action of LPS on the intestinal epithelial barrier function and tight junction proteins[J].Food & Function,2019,10(2):1235-1242.  
[19] GUO H,CALLAWAY J B,TING P Y.Inflammasomes:mechanism of action,role in disease,and therapeutics[J].Nature Medicine,2015,21(7):677-687.  
[20] KIM S J,KIM H M.Dynamic lipopolysaccharide transfer cascade to TLR4/MD2 complex via LBP and CD14[J].BMB Reports,2017,50(2):55-57.  
[21] GAY N J,SYMMONS M F,GANGLOFF M,et al.Assembly and localization of Toll-like receptor signalling complexes[J].Nature Reviews Immunology,2014,14(8):546-558.  
[22] GUVEN-MAIOROV E,KESKIN O,GURSOY A,et al.The architecture of the TIR domain signalosome in the Toll-like receptor-4 signaling pathway[J].Scientific Reports,2015,5(1):13128.
[23] TACHADO S D,ZHANG J M,ZHU J P,et al.Pneumocystis-mediated IL-8 release by macrophages requires coexpression of mannose receptors and TLR2[J].Journal of Leukocyte Biology,2007,81(1):205-211.  
[24] WESCH D,BEETZ S,OBERG H H,et al.Direct costimulatory effect of TLR3 ligand Poly(I:C) on human γδ T lymphocytes[J].The Journal of Immunology,2006,176(3):1348-1354.  
[25] LU P,SODHI C P,YAMAGUCHI Y,et al.Intestinal epithelial Toll-like receptor 4 prevents metabolic syndrome by regulating interactions between microbes and intestinal epithelial cells in mice[J].Mucosal immunology,2018,11(3):727-740.  
[26] 罗敏,肖婷婷,曾星,等.甘草酸对LPS诱导的IEC-6细胞NF-κB通路及炎症因子表达的影响[J].中国免疫学杂志,2019,35(10):1160-1163,1168.
[27] KARIN M,CLEVERS H.Reparative inflammation takes charge of tissue regeneration[J].Nature,2016,529(7586):307-315.  
[28] ATREYA I,ATREYA R,NEURATH M F.NF-κB in inflammatory bowel disease[J].Journal of Internal Medicine,2008,263(6):591-596.  
[29] PARK E Y,LEE H,PARK Y J,et al.Sulglycotide ameliorates inflammation in lipopolysaccharide-stimulated mouse macrophage cells by blocking the NF-κB signaling pathway[J].Immunopharmacology and Immunotoxicology,2019,41(4):477-484.  
[30] PARK B S,SONG D H,KIM H M,et al.The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex[J].Nature,2009,458(7242):1191-1195.  
[31] COCHET F,PERI F.The role of carbohydrates in the lipopolysaccharide (LPS)/Toll-like receptor 4(TLR4) signalling[J].International Journal of Molecular Sciences,2017,18(11):E2318.
[32] MA L,FENG L,DING X P,et al.Effect of TLR4 on the growth of SiHa human cervical cancer cells via the MyD88-TRAF6-TAK1 and NF-κB-cyclin D1-STAT3 signaling pathways[J].Oncology Letters,2018,15(3):3965-3970.
[33] HUI B,ZHANG L P,ZHOU Q H,et al.Pristimerin Inhibits LPS-triggered neurotoxicity in BV-2 microglia cells through modulating IRAK1/TRAF6/TAK1-mediated NF-κB and AP-1 signaling pathways in vitro[J].Neurotoxicity Research,2018,33(2):268-283.  
[34] NEAL M D,LEAPHART C,LEVY R,et al.Enterocyte TLR4 mediates phagocytosis and translocation of bacteria across the intestinal barrier[J].The Journal of Immunology,2006,176(5):3070-3079.  
[35] 孙丽,夏日炜,殷学梅,等.LPS诱导条件下猪小肠上皮细胞TLR4及其信号通路基因表达变化分析[J].畜牧兽医学报,2015,46(7):1095-1101.
[36] SAKAI J,CAMMAROTA E,WRIGHT J A,et al.Lipopolysaccharide-induced NF-κB nuclear translocation is primarily dependent on MyD88,but TNFα expression requires TRIF and MyD88[J].Scientific Reports,2017,7(1):1428.
[37] TANIGUCHI K,KARIN M.NF-κB,inflammation,immunity and cancer:coming of age[J].Nature Reviews Immunology,2018,18(5):309-324.  
[38] ZAMBRANO S,DE TOMA I,PIFFER A,et al.NF-κB oscillations translate into functionally related patterns of gene expression[J].eLife,2016(5):e09100.
[39] SUN S C.The non-canonical NF-κB pathway in immunity and inflammation[J].Nature Reviews Immunology,2017,17(9):545-558.  
[40] SUN S C.The noncanonical NF-κB pathway[J].Immunological Reviews,2012,246(1):125-140.  
[41] MCDANIEL D K,EDEN K,RINGEL V M,et al.Emerging roles for noncanonical NF-κB signaling in the modulation of inflammatory bowel disease pathobiology[J].Inflammatory Bowel Diseases,2016,22(9):2265-2279.  
[42] LIU Z,COLPAERT S,D'HAENS G R,et al.Hyperexpression of CD40 ligand (CD154) in inflammatory bowel disease and its contribution to pathogenic cytokine production[J].The Journal of Immunology,1999,163(7):4049-4057.
文章导航

/