Anti-inflammatory effect of Lycium barbarum on polarized human intestinal epithelial cells
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
BACKGROUND/OBJECTIVES: Inflammatory Bowel Disease (IBD) has rapidly escalated in Asia (including Korea) due to increasing westernized diet patterns subsequent to industrialization. Factors associated with endoplasmic reticulum (ER) stress are demonstrated to be one of the major causes of IBD. This study was conducted to investigate the effect of Lycium barbarum (L. barbarum) on ER stress. MATERIALS/METHODS: Mouse embryonic fibroblast (MEF) cell line and polarized Caco-2 human intestinal epithelial cells were treated with crude extract of the L. chinense fruit (LF). Paracellular permeability was measured to examine the effect of tight junction (TJ) integrity. The regulatory pathways of ER stress were evaluated in MEF knockout (KO) cell lines by qPCR for interleukin (IL) 6, IL8 and XBP1 spliced form (XBP1s). Immunoglobulin binding protein (BiP), XBP1s and CCAAT/enhancer-binding homologous protein (CHOP) expressions were measured by RT-PCR. Scanning Ion Conductance Microscopy (SICM) at high resolution was applied to observe morphological changes after treatments. RESULTS: Exposure to LF extract strengthened the TJ, both in the presence and absence of inflammation. In polarized Caco-2 pretreated with LF, induction in the expression of proinflammatory marker IL8 was not significant, whereas ER stress marker XBP1s expression was significantly increased. In wild type (wt) MEF cells, IL6, CHOP and XBP1 spliced form were dose-dependently induced when exposed to 12.5-50 μg/mL extract. However, absence of XBP1 or IRE1α in MEF cells abolished this effect. CONCLUSION: Results of this study show that LF treatment enhances the barrier function and reduces inflammation and ER stress in an IRE1α-XBP1-dependent manner. These results suggest the preventive effect of LF on healthy intestine, and the possibility of reducing the degree of inflammatory symptoms in IBD patients.
Abstract
BACKGROUND/OBJECTIVES: Inflammatory Bowel Disease (IBD) has rapidly escalated in Asia (including Korea) due to increasing westernized diet patterns subsequent to industrialization. Factors associated with endoplasmic reticulum (ER) stress are demonstrated to be one of the major causes of IBD. This study was conducted to investigate the effect of Lycium barbarum (L. barbarum) on ER stress. MATERIALS/METHODS: Mouse embryonic fibroblast (MEF) cell line and polarized Caco-2 human intestinal epithelial cells were treated with crude extract of the L. chinense fruit (LF). Paracellular permeability was measured to examine the effect of tight junction (TJ) integrity. The regulatory pathways of ER stress were evaluated in MEF knockout (KO) cell lines by qPCR for interleukin (IL) 6, IL8 and XBP1 spliced form (XBP1s). Immunoglobulin binding protein (BiP), XBP1s and CCAAT/enhancer-binding homologous protein (CHOP) expressions were measured by RT-PCR. Scanning Ion Conductance Microscopy (SICM) at high resolution was applied to observe morphological changes after treatments. RESULTS: Exposure to LF extract strengthened the TJ, both in the presence and absence of inflammation. In polarized Caco-2 pretreated with LF, induction in the expression of proinflammatory marker IL8 was not significant, whereas ER stress marker XBP1s expression was significantly increased. In wild type (wt) MEF cells, IL6, CHOP and XBP1 spliced form were dose-dependently induced when exposed to 12.5-50 μg/mL extract. However, absence of XBP1 or IRE1α in MEF cells abolished this effect. CONCLUSION: Results of this study show that LF treatment enhances the barrier function and reduces inflammation and ER stress in an IRE1α-XBP1-dependent manner. These results suggest the preventive effect of LF on healthy intestine, and the possibility of reducing the degree of inflammatory symptoms in IBD patients.
참고문헌 (44)
- Ellgaard L, "Setting the standards: quality control in the secretory pathway", Science, 286, pp.1882~1888 (1999)
- Stengel S, "Regulated proteolysis as an element of ER stress and autophagy: implications for intestinal inflammation", Biochim Biophys Acta Mol Cell Res, 1864, pp.2183~2190 (2017)
- Hampton RY, "ER stress response: getting the UPR hand on misfolded proteins", Curr Biol, 10, pp.R518~R521 (2000)
- Welihinda AA, "The unfolded protein response pathway in Saccharomyces cerevisiae. Oligomerization and trans-phosphorylation of Ire1p (Ern1p) are required for kinase activation", J Biol Chem, 271, pp.18181~18187 (1996)
- Oakes SA, "The role of endoplasmic reticulum stress in human pathology", Annu Rev Pathol, 10, pp.173~194 (2015)
- Vembar SS, "One step at a time: endoplasmic reticulumassociated degradation", Nat Rev Mol Cell Biol, 9, pp.944~957 (2008)
- Urano F, "Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1", Science, 287, pp.664~666 (2000)
- Zinszner H, "CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum", Genes Dev, 12, pp.982~995 (1998)
- Luo K, "Endoplasmic reticulum stress in intestinal epithelial cell function and inflammatory bowel disease", Gastroenterol Res Pract, 2015, pp.328791~ (2015)
- Hosomi S, "Role of endoplasmic reticulum stress and autophagy as interlinking pathways in the pathogenesis of inflammatory bowel disease", Curr Opin Gastroenterol, 31, pp.81~88 (2015)
- Ng SC, "Incidence and phenotype of inflammatory bowel disease based on results from the Asia-pacific Crohn's and colitis epidemiology study", Gastroenterology, 145, pp.158~165.e2 (2013)
- Mulder DJ, "A tale of two diseases: the history of inflammatory bowel disease", J Crohns Colitis, 8, pp.341~348 (2014)
- Cao SS, "The unfolded protein response and chemical chaperones reduce protein misfolding and colitis in mice", Gastroenterology, 144, pp.989~1000.e6 (2013)
- Dixon LJ, "Combinatorial effects of diet and genetics on inflammatory bowel disease pathogenesis", Inflamm Bowel Dis, 21, pp.912~922 (2015)
- Neish AS, "Microbes in gastrointestinal health and disease", Gastroenterology, 136, pp.65~80 (2009)
- Kaser A, "XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease", Cell, 134, pp.743~756 (2008)
- Chassaing B, "The commensal microbiota and enteropathogens in the pathogenesis of inflammatory bowel diseases", Gastroenterology, 140, pp.1720~1728 (2011)
- Cho JH, "Recent insights into the genetics of inflammatory bowel disease", Gastroenterology, 140, pp.1704~1712 (2011)
- Jostins L, "Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease", Nature, 491, pp.119~124 (2012)
- 이성희, "Intestinal Permeability Regulation by Tight Junction: Implication on Inflammatory Bowel Diseases", Intestinal research, 13(1), pp.11~18 (2015), 대한장연구학회[DOI]
- Wu GD, "Diet, the human gut microbiota, and IBD", Anaerobe, 24, pp.117~120 (2013)
- O'Sullivan M, "Nutrition in inflammatory bowel disease", Best Pract Res Clin Gastroenterol, 20, pp.561~573 (2006)
- Halmos EP, "Diets that differ in their FODMAP content alter the colonic luminal microenvironment", Gut, 64, pp.93~100 (2015)
- Gilardi D, "Complementary and alternative medicine in inflammatory bowel diseases: what is the future in the field of herbal medicine?", Expert Rev Gastroenterol Hepatol, 8, pp.835~846 (2014)
- Langhorst J, "Systematic review of complementary and alternative medicine treatments in inflammatory bowel diseases", J Crohns Colitis, 9, pp.86~106 (2015)
- Hu S, "Translational inhibition of colonic epithelial heat shock proteins by IFN-γ and TNF-α in intestinal inflammation", Gastroenterology, 133, pp.1893~1904 (2007)
- Yao R, "Quality variation of Goji (fruits of Lycium spp.) in China: a comparative morphological and metabolomic analysis", Front Pharmacol, 9, pp.151~ (2018)
- Yao R, "The genus Lycium as food and medicine: a botanical, ethnobotanical and historical review", J Ethnopharmacol, 212, pp.50~66 (2018)
- Amagase H, "A review of botanical characteristics, phytochemistry, clinical relevance in efficacy and safety of Lycium barbarum fruit (Goji)", Food Res Int, 44, pp.1702~1717 (2011)
- Chang RC, "Use of anti-aging herbal medicine, Lycium barbarum, against aging-associated diseases. What do we know so far?", Cell Mol Neurobiol, 28, pp.643~652 (2008)
- Wang CC, "Isolation of carotenoids, flavonoids and polysaccharides from Lycium barbarum L. and evaluation of antioxidant activity", Food Chem, 120, pp.184~192 (2010)
- Chan HC, "Neuroprotective effects of Lycium barbarum Lynn on protecting retinal ganglion cells in an ocular hypertension model of glaucoma", Exp Neurol, 203, pp.269~273 (2007)
- Luo Q, "Hypoglycemic and hypolipidemic effects and antioxidant activity of fruit extracts from Lycium barbarum", Life Sci, 76, pp.137~149 (2004)
- Nagpal R, "Obesitylinked gut microbiome dysbiosis associated with derangements in gut permeability and intestinal cellular homeostasis independent of diet", J Diabetes Res, 2018, pp.3462092~ (2018)
- Ferraretto A, "Morphofunctional properties of a differentiated Caco2", HT-29 co-culture as an in vitro model of human intestinal epithelium, 2018, pp.38, ~
- Garg AD, "ER stress-induced inflammation: does it aid or impede disease progression?", Trends Mol Med, 18, pp.589~598 (2012)
- Korchev YE, "Scanning ion conductance microscopy of living cells", Biophys J, 73, pp.653~658 (1997)
- Rheinlaender J, "Comparison of scanning ion conductance microscopy with atomic force microscopy for cell imaging", Langmuir, 27, pp.697~704 (2011)
- Gorelik J, "The use of scanning ion conductance microscopy to image A6 cells", Mol Cell Endocrinol, 217, pp.101~108 (2004)
- Ushiki T, "Scanning ion conductance microscopy for imaging biological samples in liquid: a comparative study with atomic force microscopy and scanning electron microscopy", Micron, 43, pp.1390~1398 (2012)
- Anariba F, "Biophysical applications of scanning ion conductance microscopy (SICM)", Mod Phys Lett B, 26, pp.1130003~ (2012)
- Gan L, "Immunomodulation and antitumor activity by a polysaccharide-protein complex from Lycium barbarum", Int Immunopharmacol, 4, pp.563~569 (2004)
- Jing L, "Evaluation of hypoglycemic activity of the polysaccharides extracted from Lycium barbarum", Afr J Tradit Complement Altern Med, 6, pp.579~584 (2009)
- Ziping Zhang, "Comparative Evaluation of the Antioxidant Effects of the Natural Vitamin C Analog 2-O-β-D-glucopyranosyl-L-ascorbic Acid Isolated from Goji Berry Fruit", Archives of Pharmacal Research, 34(5), pp.801~810 (2011), 대한약학회