Glutamate attenuates lipopolysaccharide induced intestinal barrier injury by regulating corticotropin-releasing factor pathway in weaned pigs
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Objective: The purpose of this study was to evaluate the protection of glutamate (GLU) against the impairment in intestinal barrier function induced by lipopolysaccharide (LPS) stress in weaned pigs. Methods: Twenty-four weaned pigs were divided into four treatments containing: i) non-challenged control, ii) LPS-challenged control, iii) LPS+1.0% GLU, and iv) LPS+2.0% GLU. On day 28, pigs were treated with LPS or saline. Blood samples were collected at 0, 2, and 4 h post-injection. After blood samples collection at 4 h, all pigs were slaughtered, and spleen, mesenteric lymph nodes, liver and intestinal samples were obtained. Results: Dietary GLU supplementation inhibited the LPS-induced oxidative stress in pigs, as demonstrated by reduced malondialdehyde level and increased glutathione level in jejunum. Diets supplemented with GLU enhanced villus height, villus height/crypt depth and claudin-1 expression, attenuated intestinal histology and ultrastructure impairment induced by LPS. Moreover, GLU supplementation reversed intestinal intraepithelial lymphocyte number decrease and mast cell number increase induced by LPS stress. GLU reduced serum cortisol concentration at 4 h after LPS stress and downregulated the mRNA expression of intestinal corticotropin-releasing factor signal (corticotrophin-releasing factor [CRF], CRF receptor 1 [CRFR1], glucocorticoid receptor, tryptase, nerve growth factor, tyrosine kinase receptor A), and prevented mast cell activation. GLU upregulated the mRNA expression of intestinal transforming growth factor β. Conclusion: These findings indicate that GLU attenuates LPS-induced intestinal mucosal barrier injury, which is associated with modulating CRF signaling pathway.
Abstract
Objective: The purpose of this study was to evaluate the protection of glutamate (GLU) against the impairment in intestinal barrier function induced by lipopolysaccharide (LPS) stress in weaned pigs. Methods: Twenty-four weaned pigs were divided into four treatments containing: i) non-challenged control, ii) LPS-challenged control, iii) LPS+1.0% GLU, and iv) LPS+2.0% GLU. On day 28, pigs were treated with LPS or saline. Blood samples were collected at 0, 2, and 4 h post-injection. After blood samples collection at 4 h, all pigs were slaughtered, and spleen, mesenteric lymph nodes, liver and intestinal samples were obtained. Results: Dietary GLU supplementation inhibited the LPS-induced oxidative stress in pigs, as demonstrated by reduced malondialdehyde level and increased glutathione level in jejunum. Diets supplemented with GLU enhanced villus height, villus height/crypt depth and claudin-1 expression, attenuated intestinal histology and ultrastructure impairment induced by LPS. Moreover, GLU supplementation reversed intestinal intraepithelial lymphocyte number decrease and mast cell number increase induced by LPS stress. GLU reduced serum cortisol concentration at 4 h after LPS stress and downregulated the mRNA expression of intestinal corticotropin-releasing factor signal (corticotrophin-releasing factor [CRF], CRF receptor 1 [CRFR1], glucocorticoid receptor, tryptase, nerve growth factor, tyrosine kinase receptor A), and prevented mast cell activation. GLU upregulated the mRNA expression of intestinal transforming growth factor β. Conclusion: These findings indicate that GLU attenuates LPS-induced intestinal mucosal barrier injury, which is associated with modulating CRF signaling pathway.
참고문헌 (43)
- Otani S, "Gut integrity in critical illness", J Intensive Care, 7, pp.17~ (2019)[DOI]
- Vanuytsel T, "Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism", Gut, 63, pp.1293~1299 (2014)[DOI]
- Galesi FL, "Role of Hypothalamic-Pituitary-Adrenal axis and corticotropin-releasing factor stress system on cue-induced relapse to alcohol seeking", Eur J Pharmacol, 788, pp.84~89 (2016)[DOI]
- Neurath MF, "New targets for mucosal healing and therapy in inflammatory bowel diseases", Mucosal Immunol, 7, pp.6~19 (2014)[DOI]
- Christianne Maria Tinoco-Veras, "Transforming Growth Factor β1", SMAD Signaling Pathway Activation Protects the Intestinal Epithelium from Clostridium difficile Toxin A-Induced Damage, 2017, pp.85(10), e00430-17~[DOI]
- Song HP, "Atractylenolide I stimulates intestinal epithelial repair through polyamine-mediated Ca2+ signaling pathway", Phytomedicine, 28, pp.27~35 (2017)[DOI]
- Lan A, "Mucosal healing in inflammatory bowel diseases : is there a place for nutritional supplementation?", Inflamm Bowel Dis, 21, pp.198~207 (2015)[DOI]
- Schunemann DP, "Glutamate promotes cell growth by EGFR signaling on U-87MG human glioblastoma cell line", Pathol Oncol Res, 16, pp.285~293 (2010)[DOI]
- Blachier F, "Metabolism and functions of L-glutamate in the epithelial cells of the small and large intestines", Am J ClinNutr, 90, pp.814S~821S (2009)[DOI]
- Wu G, "Functional amino acids in growth, reproduction and health", Adv Nutr, 1, pp.31~37 (2010)[DOI]
- Soszynski D, "The inhibition of nitric oxide synthase suppresses LPS-and psychological-stress-induced fever in rats", Physiol Behav, 72, pp.65~72 (2001)[DOI]
- Guilloteau P, "Nutritional programming of gastrointestinal tract development. Is the pig a good model for man?", Nutr Res Rev, 23, pp.4~22 (2010)[DOI]
- Kang P, "Glutamate alleviates muscle protein loss by modulating TLR4, NODs, Akt", FOXO and mTOR signaling pathways in LPS-challenged piglets, 2017, pp.12, e0182246~
- Yang RK, "IL-6 is essential for development of gut barrier dysfunction after hemorrhagic shock and resuscitation in mice", Am J Physiol Gastrointest Liver Physiol, 285, pp.G621~G629 (2003)[DOI]
- Livak KJ, "Analysis of relative gene expression data using real-time quantitative PCR and 2 (Delta Delta C (T)) method", Methods, 25, pp.402~408 (2001)[DOI]
- Brosnan JT, "Glutamate : a truly functional amino acid", Amino Acids, 45, pp.413~418 (2013)[DOI]
- Levite M, "Glutamate, T cells and multiple sclerosis", J Neural Transm(Vienna), 124, pp.775~798 (2017)[DOI]
- Rezaei R, "Dietary supplementation with monosodium glutamate is safe and improves growth performance in postweaning pigs", Amino Acids, 44, pp.911~923 (2013)[DOI]
- Song ZH, "L-Cysteine protects intestinal integrity, attenuates intestinal inflammation and oxidant stress, and modulates NF-κB and Nrf2 pathways in weaned piglets after LPS challenge", Innate Immun, 22, pp.152~161 (2016)[DOI]
- Qiu YQ, "L-Arginine inhibited inflammatory response and oxidative stress induced by lipopolysaccharide via arginase-1 signaling in IPEC-J2cells", Int J Mol Sci, 20, pp.1800~ (2019)[DOI]
- Sies H, "Oxidative stress : From basic research to clinical application", Am J Med, 91, pp.31S~38S (1991)[DOI]
- Duan JL, "Dietary supplementation with L-glutamate and L-aspartate alleviates oxidative stress in weaned piglets challenged with hydrogen peroxide", Amino Acids, 48, pp.53~64 (2016)[DOI]
- Xiao W, "Glutamate prevents intestinal atrophy via luminal nutrient sensing in a mouse model of total parenteral nutrition", FASEB J, 28, pp.2073~2087 (2014)[DOI]
- Duan JL, "Dietary glutamate supplementation ameliorates mycotoxin-induced abnormalities in the intestinal structure and expression of amino acid transporters in young pigs", PLOS ONE, 9, pp.e112357~ (2014)[DOI]
- Jing J, "Glutamate attenuates lipopolysaccharide-induced oxidative damage and mRNA expression changes of tight junction and defensin proteins, inflammatory and apoptosis response signaling molecules in the intestine of fish", Fish Shellfish Immunol, 70, pp.473~484 (2017)[DOI]
- Ulluwishewa D, "Regulation of tight junction permeability by intestinal bacteria and dietary components", J Nutr, 141, pp.769~776 (2011)[DOI]
- Jiao N, "L-glutamate enhances barrier and antioxidative functions in intestinal porcine epithelial cells", J Nutr, 145, pp.2258~2264 (2015)[DOI]
- Wu L, "Dietary L-arginine supplementation protects weanling pigs from deoxynivalenol-induced toxicity", Toxins(Basel), 7, pp.1341~1354 (2015)[DOI]
- Wu X, "The acute and chronic effects of monosodium L-glutamate on serum iron and total ironbinding capacity in the jugular artery and vein of pigs", Biol Trace Elem Res, 153, pp.191~195 (2013)[DOI]
- Moore KA, "Stem cells and their niches", Science, 311, pp.1880~1885 (2006)[DOI]
- Corpeleijn WE, "Almost all enteral aspartate is taken up in first-pass metabolism in enterally fed preterm infants", Clin Nutr, 29, pp.341~346 (2010)[DOI]
- Tomé D, "The roles of dietary glutamate in the intestine", Ann Nutr Metab, 73(Suppl. 5), pp.15~20 (2018)[DOI]
- Ruth MR, "The immune modifying effects of amino acids on gut-associated lymphoid tissue", J Anim Sci Biotechnol, 4, pp.27~ (2013)[DOI]
- Akiba Y, "Luminal L-glutamate enhances duodenal mucosal defense mechanisms via multiple glutamate receptors in rats", Am J Physiol Gastroinstest Liver Physiol, 297, pp.G781~G91 (2009)[DOI]
- Smith F, "Early weaning stress impairs development of mucosal barrier function in the porcine intestine", Am J Physiol Gastrointest Liver Physiol, 298, pp.G352~G363 (2010)[DOI]
- Theoharides TC, "Mast cells as targets of corticotropinreleasing factor and related peptides", Trends PharmacolSci, 25, pp.563~568 (2004)[DOI]
- Meddings JB, "Environmental stress-induced gastrointestinal permeability is mediated by endogenous glucocorticoids in the rat", Gastroenterology, 119, pp.1019~1028 (2000)[DOI]
- Wang H, "Glutamine enhances tight junction protein expression and modulates corticotropinreleasing factor signaling in the jejunum of weanling piglets", J Nutr, 145, pp.25~31 (2015)[DOI]
- Barreau F, "Nerve growth factor mediates alterations of colonic sensitivity and mucosal barrier induced by neonatal stress in rats", Gastroenterology, 127, pp.524~534 (2004)[DOI]
- Dothel G, "Nerve fiber outgrowth is increased in the intestinal mucosa of patients with irritable bowel syndrome", Gastroenterology, 148, pp.1002~1011 (2015)[DOI]
- Chen X, "Differentiation and proliferation of intestinal stem cells and its underlying regulated mechanisms during weaning", Curr Protein Pept Sci, 20, pp.690~695 (2019)[DOI]
- Xiao K, "Developmental changes of TGF-β1 and Smads signaling pathway in intestinal adaption of weaned pigs", PLoS ONE, 9, pp.e104589~ (2014)[DOI]
- Qin Q, "Glutamate alleviates intestinal injury, maintains mTOR and suppresses TLR4 and NOD signaling pathways in weanling pigs challenged with lipopolysaccharide", Sci Rep, 8, pp.15124~ (2018)[DOI]
