Vitamin A inhibits the action of LPS on the intestinal epithelial barrier function and tight junction proteins

被引:167
作者
He, Caimei [1 ]
Deng, Jun [1 ]
Hu, Xin [1 ]
Zhou, Sichun [1 ]
Wu, Jingtao [1 ]
Xiao, Di [1 ]
Darko, Kwame Oteng [1 ]
Huang, Yanjun [1 ]
Tao, Ting [1 ]
Peng, Mei [1 ,2 ]
Wang, Zhiren [1 ]
Yang, Xiaoping [1 ]
机构
[1] Hunan Normal Univ, Sch Med, Dept Pharm, Key Lab Study & Discovery Small Targeted Mol Huna, Changsha, Hunan, Peoples R China
[2] Cent S Univ, Xiangya Hosp, Dept Pharm, Changsha, Hunan, Peoples R China
关键词
NF-KAPPA-B; RETINOIC ACID; PERMEABILITY; MODULATION; ACTIVATION; DISEASE;
D O I
10.1039/c8fo01123k
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Inflammation caused by either intrinsic or extrinsic toxins results in intestinal barrier dysfunction, contributing to inflammatory bowel disease (IBD) and other diseases. Vitamin A is a widely used food supplement although its mechanistic effect on intestinal structures is largely unknown. The goal of this study was to explore the mechanism by investigating the influence of vitamin A on the intestinal barrier function, represented by tight junctions. IPEC-J2 cells were differentiated on transwell inserts and used as a model of intestinal barrier permeability. Transepithelial electrical resistance (TEER) was used as an indicator of monolayer integrity and paracellular permeability. Western blot and the reverse transcriptase-polymerase chain reaction were used to assess the protein and mRNA expression of tight junction proteins. Immunofluorescence microscopy was used to evaluate the localization and expression of tight junctions. Differentiated cells were treated with a vehicle control (Ctrl), inflammatory stimulus (1 g mL(-1) LPS), LPS co-treatment with 0.1 mol L-1 Vitamin A (1 g mL(-1) LPS + 0.1 mol L-1 VA) and 0.1 mol L-1 Vitamin A. LPS significantly decreased TEER by 24 hours, continuing this effect to 48 hours after application. Vitamin A alleviated the LPS-induced decrease of TEER from 12 hours to 48 hours, while Vitamin A alone enhanced TEER, indicating that Vitamin A attenuated LPS-induced intestinal epithelium permeability. Mechanistically, different concentrations of Vitamin A (0-20 mol L-1) enhanced tight junction protein markers including Zo-1, Occludin and Claudin-1 both at protein and mRNA levels with an optimized dose of 0.1 mol L-1. Immunofluorescence results demonstrated that majority of Zo-1 and Claudin-1 is located at the tight junctions, as we expected. LPS reduced the expression of these proteins and Vitamin A reversed LPS-reduced expression of these proteins, consistent with the results of western blot. In conclusion, Vitamin A improves the intestinal barrier function and reverses LPS-induced intestinal barrier damage via enhancing the expression of tight junction proteins.
引用
收藏
页码:1235 / 1242
页数:8
相关论文
共 33 条
[1]   TNF-α Modulation of Intestinal Tight Junction Permeability Is Mediated by NIK/IKK-α Axis Activation of the Canonical NF-κB Pathway [J].
Al-Sadi, Rana ;
Guo, Shuhong ;
Ye, Dongmei ;
Rawat, Manmeet ;
Ma, Thomas Y. .
AMERICAN JOURNAL OF PATHOLOGY, 2016, 186 (05) :1151-1165
[2]   TIGHT JUNCTIONS AND THE MOLECULAR-BASIS FOR REGULATION OF PARACELLULAR PERMEABILITY [J].
ANDERSON, JM ;
VANITALLIE, CM .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 1995, 269 (04) :G467-G475
[3]   Endothelial cell-to-cell junctions: Molecular organization and role in vascular homeostasis [J].
Bazzoni, G ;
Dejana, E .
PHYSIOLOGICAL REVIEWS, 2004, 84 (03) :869-901
[4]   Layered defense: how mucus and tight junctions seal the intestinal barrier [J].
Capaldo, Christopher T. ;
Powell, Domonica N. ;
Kalman, Daniel .
JOURNAL OF MOLECULAR MEDICINE-JMM, 2017, 95 (09) :927-934
[5]   Protective Effect of 1,25-Dihydroxyvitamin D3 on Lipopolysaccharide-Induced Intestinal Epithelial Tight Junction Injury in Caco-2 Cell Monolayers [J].
Chen, Shan-Wen ;
Wang, Peng-Yuan ;
Zhu, Jing ;
Chen, Guo-Wei ;
Zhang, Jun-Ling ;
Chen, Zi-Yi ;
Zuo, Shuai ;
Liu, Yu-Cun ;
Pan, Yi-Sheng .
INFLAMMATION, 2015, 38 (01) :375-383
[6]   Vitamin A supplementation increases ratios of proinflammatory to anti-inflammatory cytokine responses in pregnancy and lactation [J].
Cox, S. E. ;
Arthur, P. ;
Kirkwood, B. R. ;
Yeboah-Antwi, K. ;
Riley, E. M. .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2006, 144 (03) :392-400
[7]   Total Lipopolysaccharide from the Human Gut Microbiome Silences Toll-Like Receptor Signaling [J].
d'Hennezel, Eva ;
Abubucker, Sahar ;
Murphy, Leon O. ;
Cullen, Thomas W. .
MSYSTEMS, 2017, 2 (06)
[8]   Modulation of Intestinal Immune and Barrier Functions by Vitamin A: Implications for Current Understanding of Malnutrition and Enteric Infections in Children [J].
de Medeiros, Pedro Henrique Q. S. ;
Pinto, Daniel V. ;
de Almeida, Juliana Zani ;
Rego, Juliana M. C. ;
Rodrigues, Francisco A. P. ;
Lima, Aldo Angelo M. ;
Bolick, David T. ;
Guerrant, Richard L. ;
Oria, Reinaldo B. .
NUTRIENTS, 2018, 10 (09)
[9]   Intestinal Permeability and Its Regulation by Zonulin: Diagnostic and Therapeutic Implications [J].
Fasano, Alessio .
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, 2012, 10 (10) :1096-1100
[10]   Tight junctions and the modulation of barrier function in disease [J].
Foerster, Carola .
HISTOCHEMISTRY AND CELL BIOLOGY, 2008, 130 (01) :55-70