Journal of Shandong University (Health Sciences) ›› 2022, Vol. 60 ›› Issue (9): 67-73.doi: 10.6040/j.issn.1671-7554.0.2022.0686

Previous Articles     Next Articles

Changes of intestinal B lymphocytes in 6 mice with non-alcoholic fatty liver disease

ZHANG Feng, WU Zhe, XU Jun, LIU Yulan   

  1. Department of Gastroenterology, Peking University Peoples Hospital, Beijing 100044, China
  • Published:2022-09-02

PDF (PC)

130

Abstract: Objective To investigate the changes of intestinal B lymphocytes in mice with non-alcoholic fatty liver disease(NAFLD)induced by high fat diet. Methods A total of 12 male C57BL/6J mice were randomly divided into the experimental group and control group, with 6 in either group. The experimental group was fed with 45% high fat diet, while the control group with normal diet. After 16 weeks, the mice were killed to collect liver, small intestine mucosa, colon mucosa, mesenteric lymph nodes(MLN), Peyers patches(PP)and small intestine contents. Hepatic steatosis in experimental group was confirmed with hematoxylin and eosin(HE)staining. The distribution and expression of B cells in small intestine and colon mucosa were detected with immunohistochemical staining and real-time quantitative PCR, respectively. Proportion of B and T lymphocytes in the MLN and PP were analyzed with flow cytometry. The sIgA level in the small intestinal contents was detected with enzyme linked immunosorbent assay(ELISA). B lymphocytes were enriched with a magnetic-activated cell sorting method and cultured in vitro with or without the stimulation of lipopolysaccharide(LPS)or anti-CD40/IgM(BCR). The levels of IL-6, IL-10 and TNF-α in the cultural supernatants were monitored with cytometric bead arrays(CBA). Results B lymphocytes scattered throughout the lamina in both groups. The proportion of B lymphocytes was increased significantly in MLN and PP in experimental group than in control group(PMLN-B=0.025, PPP-B=0.004). The experimental group had higher level of sIgA in the small intestinal contents(P=0.042), which was in line with the higher proportion of IgA+ B lymphocytes in the PP(P=0.023). B lymphocytes in MLN in the experimental group secreted more IL-6 upon the stimulation of LPS or anti-CD40/IgM(BCR)(PLPS<0.001, PBCR=0.003)than in the control group. Conclusion Proportion of B lymphocytes in PP and MLN increased significantly in NAFLD mice. Small intestine secreted higher level of sIgA, and B lymphocytes in MLN produced more IL-6 upon stimulation in NAFLD mice.

Key words: Non-alcoholic fatty liver disease, B lymphocyte, Gut, Gut-liver axis, Inflammatory cytokine

CLC Number: 

  • R575
[1] Younossi Z, Tacke F, Arrese M, et al. Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[J]. Hepatology, 2019, 69(6): 2672-2682.
[2] Fan JG, Kim SU, Wong VW. New trends on obesity and NAFLD in Asia[J]. J Hepatol, 2017, 67(4): 862-873.
[3] Zhu J, Xu D, Yang R, et al. The triglyceride glucose index(TyG)and CDKAL1 gene rs10946398 SNP are associated with NAFLD in Chinese adults[R]. Minerva Endocrinol, 2020. doi: 10.23736/S0391-1977.20.03273-3.
[4] Day CP, James OF. Steatohepatitis: a tale of two “hits” ?[J]. Gastroenterology, 1998, 114(4): 842-845.
[5] Tilg H, Moschen AR. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis[J]. Hepatology, 2010, 52(5): 1836-1846.
[6] Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease[J]. Nat Rev Microbiol, 2021, 19(1): 55-71.
[7] Milosevic I, Vujovic A, Barac A, et al. Gut-liver axis, gut microbiota, and its modulation in the management of liver diseases: a review of the literature[J]. Int J Mol Sci, 2019, 20(2): E395.
[8] Ahluwalia B, Magnusson MK, Öhman L. Mucosal immune system of the gastrointestinal tract: maintaining balance between the good and the bad[J]. Scand J Gastroenterol, 2017, 52(11): 1185-1193.
[9] Tourkochristou E, Triantos C, Mouzaki A. The influence of nutritional factors on immunological outcomes[J]. Front Immunol, 2021, 12: 665968. doi: 10.3389/fimmu.2021.665968.
[10] Marshall JC. The gut as a potential trigger of exercise-induced inflammatory responses[J]. Can J Physiol Pharmacol, 1998, 76(5): 479-484.
[11] Schroeder BO. Fight them or feed them: how the intestinal mucus layer manages the gut microbiota[J]. Gastroenterol Rep(Oxf), 2019, 7(1): 3-12.
[12] Volynets V, Küper MA, Strahl S, et al. Nutrition, intestinal permeability, and blood ethanol levels are altered in patients with nonalcoholic fatty liver disease(NAFLD)[J]. Dig Dis Sci, 2012, 57(7): 1932-1941.
[13] Briskey D, Heritage M, Jaskowski LA, et al. Probiotics modify tight-junction proteins in an animal model of nonalcoholic fatty liver disease[J]. Therap Adv Gastroenterol, 2016, 9(4): 463-472.
[14] Castoldi A, Favero de Aguiar C, Moraes-Vieira PM, et al. They must hold tight: junction proteins, microbiota and immunity in intestinal mucosa[J]. Curr Protein Pept Sci, 2015, 16(7): 655-671.
[15] Jiang W, Wu N, Wang X, et al. Dysbiosis gut microbiota associated with inflammation and impaired mucosal immune function in intestine of humans with non-alcoholic fatty liver disease[J]. Sci Rep, 2015, 5: 8096. doi: 10.1038/srep08096.
[16] Ferro D, Baratta F, Pastori D, et al. New insights into the pathogenesis of non-alcoholic fatty liver disease: gut-derived lipopolysaccharides and oxidative stress[J]. Nutrients, 2020, 12(9): E2762.
[17] Kolodziejczyk AA, Zheng D, Shibolet O, et al. The role of the microbiome in NAFLD and NASH[J]. EMBO Mol Med, 2019, 11(2): e9302.
[18] Mörbe UM, Jrgensen PB, Fenton TM, et al. Human gut-associated lymphoid tissues(GALT); diversity, structure, and function[J]. Mucosal Immunol, 2021, 14(4): 793-802.
[19] Muniz LR, Knosp C, Yeretssian G. Intestinal antimicrobial peptides during homeostasis, infection, and disease[J]. Front Immunol, 2012, 3: 310. doi: 10.3389/fimmu.2012.00310.
[20] Chairatana P, Nolan EM. Defensins, lectins, mucins, and secretory immunoglobulin a: microbe-binding biomolecules that contribute to mucosal immunity in the human gut[J]. Crit Rev Biochem Mol Biol, 2017, 52(1): 45-56.
[21] Mohamad Nor MH, Ayob N, Mokhtar NM, et al. The effect of probiotics(MCP® BCMC® strains)on hepatic steatosis, small intestinal mucosal immune function, and intestinal barrier in patients with non-alcoholic fatty liver disease[J]. Nutrients, 2021, 13(9): 3192.
[22] Palm NW, de Zoete MR, Cullen TW, et al. Immunoglobulin a coating identifies colitogenic bacteria in inflammatory bowel disease[J]. Cell, 2014, 158(5): 1000-1010.
[23] Cobbina E, Akhlaghi F. Non-alcoholic fatty liver disease(NAFLD)- pathogenesis, classification, and effect on drug metabolizing enzymes and transporters[J]. Drug Metab Rev, 2017, 49(2): 197-211.
[24] Akbari R, Behdarvand T, Afarin R, et al. Saroglitazar improved hepatic steatosis and fibrosis by modulating inflammatory cytokines and adiponectin in an animal model of non-alcoholic steatohepatitis[J]. BMC Pharmacol Toxicol, 2021, 22(1): 53.
[25] Van Herck MA, Weyler J, Kwanten WJ, et al. The differential roles of T cells in non-alcoholic fatty liver disease and obesity[J]. Front Immunol, 2019, 10: 82. doi: 10.3389/fimmu.2019.00082.
[26] Winer DA, Winer S, Shen L, et al. B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies[J]. Nat Med, 2011, 17(5): 610-617.
[27] DeFuria J, Belkina AC, Jagannathan-Bogdan M, et al. B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile[J]. PNAS, 2013, 110(13): 5133-5138.
[1] LI Rui, SHI Cunxian, YU Cuicui. Effects of dexmedetomidine on intestinal-related injury during cardiopulmonary bypass [J]. Journal of Shandong University (Health Sciences), 2022, 60(7): 83-88.
[2] ZHANG Weiwei, HUA Fang, LIANG Chaoshuai, CHU Miaomiao, SUN Jiayi, FRANK Zaucke, XIN Wei. Thyroid stimulating hormone promotes chondrocyte differentiation via anti-inflammatory protein CTRP3 [J]. Journal of Shandong University (Health Sciences), 2022, 60(10): 1-8.
[3] LOU Fuchen, LIU Xingxiang, MA Guoyun, ZHUANG Xianghua. Effects of acarbose on YKL-40 and gut bacteria in coronary heart disease patients with impaired glucose tolerance [J]. Journal of Shandong University (Health Sciences), 2019, 57(7): 86-91.
[4] WANG Guoyun, YUAN Ming, JI Miaomiao. Research advances in the pathogenesis of endometriosis [J]. Journal of Shandong University (Health Sciences), 2019, 57(6): 33-39.
[5] YANG Yanjun, LIANG Jing, LI Fang, DU Lingxi. Effect of halofuginone on macrophage polarization in endometriosis mouse [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(9): 26-31.
[6] SHEN Zhenwei, JI Xiaokang, WANG Qinglian, LI Jie, XUE Fuzhong, LIU Jing. Association between nonalcoholic fatty liver disease and chronic kidney disease: a retrospective cohort study [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(7): 43-49.
[7] WANG Qingshi, CHEN Yunzhen, LIU Haichun, WU Wenliang, JIAO Guangjun, LI Xiaofeng, XU Daxia. Effects of inflammatory cytokines secreted by nucleus pulposus cells on proliferation and osteogenic ability of posterior longitudinal ligament fibroblasts [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(6): 22-26.
[8] CAO Jing, CHEN Feixue, WANG Tengfei, ZHAO Hongyu, ZHAO Dongyan, ZUO Xiuli, LI Yanqing. Effects of brain-derived neurotrophic factor on colon smooth muscle cells and the mechnism in mice [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(12): 1-6.
[9] SUI Xiangyu, ZHANG Xiangchun, ZHANG Guangyong, HU Sanyuan, WANG Yanlei, DAI Yong. Preliminary study in the protective role of p120 catenin in inflammatory lung injury [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(12): 41-44.
[10] PENG Xiao-nu1，2， LI Wen-jun2， TIAN Hui1. Poly(ADP-ribose) polymerase 1 inhibition protects human bronchial endothelial cells against nicotineinduced inflammation response [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(2): 37-43.
[11] ZHU Yue-ting1， JIAO Yu-lian2， CUI Bin2， ZHANG Jie2， YOU Li2， ZHAO Yue-ran1,2. Expression of the fusion protein of human soluble B lymphocyte stimulator  and diphtheria toxin in E.coli and its biological activity [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2011, 49(7): 48-52.
[12] SHI Wen, XIN Nai-Jun, MA Yin-Dong, YANG Tao, JIA Jun, JIANG Jin-Zhu, GUO Cheng-Hao, SONG Guo-Dong. Effect of recombinant human growth hormone on intestinal mucosal cellular apoptosis in severely scalded rats [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2009, 47(5): 59-62.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] SUO Dongyang, SHEN Fei, GUO Hao, LIU Lichang, YANG Huimin, YANG Xiangdong. Expression and mechanism of Tim-3 in animal model of drug-induced acute kidney injury[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 1 -6 .
[2] MA Qingyuan, PU Peidong, HAN Fei, WANG Chao, ZHU Zhoujun, WANG Weishan, SHI Chenhui. Effect of miR-27b-3p regulating SMAD1 on osteosarcoma cell proliferation, migration and invasion[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 32 -37 .
[3] ZHANG Baowen, LEI Xiangli, LI Jinna, LUO Xiangjun, ZOU Rong. miR-21-5p targeted TIMP3 to inhibit proliferation and extracellular matrix accumulation of mesangial cells in Type II diabetic nephropathy mice[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 7 -14 .
[4] FU Jieqi, ZHANG Man, ZHANG Xiaolu, LI Hui, CHEN Hong. Molecular mechanism of Toll-like receptor 4 in the aggravation of blood lipid accumulation by inhibiting the peroxisome proliferator-activate receptor γ[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 24 -31 .
[5] LONG Tingting, XIE Ming, ZHOU Lu, ZHU Junde. Effect of Noggin protein on learning and memory abilities and the dentate gyrus structure after cerebral ischemia reperfusion injury in mice[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 15 -23 .
[6] LI Ning, LI Juan, XIE Yan, LI Peilong, WANG Yunshan, DU Lutao, WANG Chuanxin. Expression of LncRNA AL109955.1 in 80 cases of colorectal cancer and its effect on cell proliferation, migration and invasion[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 38 -46 .
[7] XU Yuxiang, LIU Yudong, ZHANG Peng, DUAN Ruisheng. A retrospective analysis of risk factors of cerebral microbleeds in 101 patients with cerebral small vessel disease[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 67 -71 .
[8] DING Xiangyun, YU Qingmei, ZHANG Wenfang, ZHUANG Yuan, HAO Jing. Correlation of the expression of insulin-like growth factor II in granulosa cells and ovulation induction outcomes of 84 patients with polycystic ovary syndrome[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 60 -66 .
[9] XIAO Juan, XIAO Qiang, CONG Wei, LI Ting, DING Shouluan, ZHANG Yuan, SHAO Chunchun, WU Mei, LIU Jianing, JIA Hongying. Comparison of diagnostic efficacy of two kinds of thyroid imagine reporting and data systems[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 53 -59 .
[10] SHI Shuang, LI Juan, MI Qi, WANG Yunshan, DU Lutao, WANG Chuanxin. Construction and application of a miRNAs prognostic risk assessment model of gastric cancer[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 47 -52 .
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd