IL-17A knockout alleviates lipopolysaccharide-induced steatotic liver injury in mice

Wei XIANG; Xiaodong WANG; Zhengyan LI; Bin XIE; Lixia GAN

doi:10.16016/j.1000-5404.201701092

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IL-17A knockout alleviates lipopolysaccharide-induced steatotic liver injury in mice

更新时间：2026-01-09

- IL-17A knockout alleviates lipopolysaccharide-induced steatotic liver injury in mice
- Journal of Third Military Medical University Vol. 39, Issue 16, Pages: 1599-1605(2017)
- 作者机构：
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81270482)
- DOI：10.16016/j.1000-5404.201701092
  CLC：
- Received：11 January 2017，
  
  Published：30 August 2017
- 稿件说明：
移动端阅览
Wei XIANG, Xiaodong WANG, Zhengyan LI, et al. IL-17A knockout alleviates lipopolysaccharide-induced steatotic liver injury in mice[J]. Journal of Third Military Medical University, 2017, 39(16): 1599-1605.
DOI：

Wei XIANG, Xiaodong WANG, Zhengyan LI, et al. IL-17A knockout alleviates lipopolysaccharide-induced steatotic liver injury in mice[J]. Journal of Third Military Medical University, 2017, 39(16): 1599-1605. DOI： 10.16016/j.1000-5404.201701092.

摘要

Abstract

Objective

To investigate the effect of interleukin 17A (IL-17A)deficiency on lipopolysaccharide(LPS)-induced liver injury in mice with long-term high fat diet feeding and explore the underlying mechanism.

Methods

C57BL/6 mice with IL-17A gene knockout (KO) and the wild-type (WT) littermates fed with high fat diet for 3 months were given an intraperitoneal injection of 4 mg/kg lipopolysaccharide (LPS). Plasma levels of alanine transaminase(ALT) and aspartate transaminase (AST) were detected to assess liver injury. Plasma TNF-α

IL-1β and IL-6 levels were determined to assess the severity of inflammation. Inflammatory cell infiltration in the liver and the impairment of hepatic cells were observed. The liver tissues from the WT and KO mice were subjected to transcriptomic analysis to study the effect of IL-17A deficiency on high-fat-diet-and LPS-induced liver injuries.

Results

High fat diet feeding and LPS challenge significantly decreased the plasma ALT and AST levels in IL-17A KO mice (

0.05). In the KO mice

the plasma levels of inflammatory cytokines and the number of infiltrating inflammatory cells in the liver were reduced significantly(

0.05). Transcriptomic analysis showed that 938 genes were down-regulated in the KO mice after LPS stimulation

among which the genes involved in oxidation reduction process(

0.01)

hydrogen peroxide metabolic process (

0.01)

and glutathione metabolic process (

0.01) showed the most significant decreases. Real-time PCR demonstrated that a panel of metabolic enzymes participated in hydrogen peroxide detoxification

such as CAT

GPX1

IDH1

IDH2 and ME1

which were highly expressed in the KO mice (

0.05). The levels of reactive oxygen species (ROS) were significantly decreased in the liver of KO mice (

0.05). TUNEL assay indicated that the number of apoptotic cells was significantly reduced in the liver of KO mice(

0.05).

Conclusion

IL-17A deficiency may alleviate LPS-induced acute inflammatory injury in fatty liver mice by reducing hepatic ROS accumulation.

关键词

Keywords

references

LI Z XUE J CHEN P Prevalence of nonalcoholic fatty liver disease in mainland of China: a meta-analysis of published studies J Gastroenterol Hepatol 2014 29 1 42 51 10.1111/jgh.12428 LI Z, XUE J, CHEN P, et al . Prevalence of nonalcoholic fatty liver disease in mainland of China: a meta-analysis of published studies[J ] . J Gastroenterol Hepatol, 2014, 29(1): 42-51. DOI: 10.1111/jgh.12428.

FAN J G Epidemiology of alcoholic and nonalcoholic fatty liver disease in China J Gastroenterol Hepatol 2013 28 Suppl 1 11 17 10.1111/jgh.12036 FAN J G. Epidemiology of alcoholic and nonalcoholic fatty liver disease in China[J]. J Gastroenterol Hepatol, 2013, 28(Suppl 1): 11-17. DOI: 10.1111/jgh.12036.

OO Y H BANZ V KAVANAGH D CXCR3-dependent recruitment and CCR6-mediated positioning of Th-17 cells in the inflamed liver J Hepatol 2012 57 5 1044 1051 10.1016/j.jhep.2012.07.008 OO Y H, BANZ V, KAVANAGH D, et al . CXCR3-dependent recruitment and CCR6-mediated positioning of Th-17 cells in the inflamed liver[J ] . J Hepatol, 2012, 57(5): 1044-1051. DOI: 10.1016/j.jhep.2012.07.008.

ZHANG J Y ZHANG Z LIN F Interleukin-17-producing CD4(+) T cells increase with severity of liver damage in patients with chronic hepatitis B Hepatology 2010 51 1 81 91 10.1002/hep.23273 ZHANG J Y, ZHANG Z, LIN F, et al . Interleukin-17-producing CD4(+) T cells increase with severity of liver damage in patients with chronic hepatitis B[J ] . Hepatology, 2010, 51(1): 81-91. DOI: 10.1002/hep.23273.

TANG Y BIAN Z ZHAO L Interleukin-17 exacerbates hepatic steatosis and inflammation in non-alcoholic fatty liver disease Clin Exp Immunol 2011 166 2 281 290 10.1111/j.1365-2249.2011.04471.x TANG Y, BIAN Z, ZHAO L, et al . Interleukin-17 exacerbates hepatic steatosis and inflammation in non-alcoholic fatty liver disease[J ] . Clin Exp Immunol, 2011, 166(2): 281-290. DOI: 10.1111/j.1365-2249.2011.04471.x.

HARLEY I T STANKIEWICZ T E GILES D A IL-17 signaling accelerates the progression of nonalcoholic fatty liver disease in mice Hepatology 2014 59 5 1830 1839 10.1002/hep.26746 HARLEY I T, STANKIEWICZ T E, GILES D A, et al . IL-17 signaling accelerates the progression of nonalcoholic fatty liver disease in mice[J ] . Hepatology, 2014, 59(5): 1830-1839. DOI: 10.1002/hep.26746.

ZHANG L ZHANG F K Advances in research of nonalcoholic fatty liver disease World Chin J Digestol 2016 27 3860 3869 10.11569/wcjd.v24.i27.3860 ZHANG L, ZHANG F K. Advances in research of nonalcoholic fatty liver disease[J].World Chin J Digestol, 2016(27): 3860-3869. DOI: 10.11569/wcjd.v24.i27.3860.

DAY C P JAMES O F Steatohepatitis: a tale of two "hits"? Gastroenterology 1998 114 4 842 845 10.1016/S0016-5085(98)70599-2 DAY C P, JAMES O F. Steatohepatitis: a tale of two "hits"?[J]. Gastroenterology, 1998, 114(4): 842-845.

TESSARI P CORACINA A COSMA A Hepatic lipid metabolism and non-alcoholic fatty liver disease Nutr Metab Cardiovasc Dis 2009 19 4 291 302 10.1016/j.numecd.2008.12.015 TESSARI P, CORACINA A, COSMA A, et al . Hepatic lipid metabolism and non-alcoholic fatty liver disease[J ] . Nutr Metab Cardiovasc Dis, 2009, 19(4): 291-302. DOI: 10.1016/j.numecd.2008.12.015.

LAMBERT J E RAMOS-ROMAN M A Browning J D Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease Gastroenterology 2014 146 3 726 735 10.1053/j.gastro.2013.11.049 LAMBERT J E, RAMOS-ROMAN M A, Browning J D, et al . Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease[J ] . Gastroenterology, 2014, 146(3): 726-735. DOI: 10.1053/j.gastro.2013.11.049.

KOUKIAS N BUZZETTI E TSOCHATZIS E A Intestinal hormones, gut microbiota and nonalcoholic fatty liver disease Minerva Endocrinologica 2017 42 2 184 194 http://www.minervamedica.it/en/journals/minerva-endocrinologica/article.php?cod=R07Y2017N02A0184 KOUKIAS N, BUZZETTI E, TSOCHATZIS E A. Intestinal hormones, gut microbiota and nonalcoholic fatty liver disease[J]. Minerva Endocrinologica, 2017. 42(2): 184-194.

PATTERSON R E KALAVALAPALLI S WILLIAMS C M Lipotoxicity in steatohepatitis occurs despite an increase in tricarboxylic acid cycle activity Am J Physiol Endocrinol Metab 2016 310 7 E484 E494 10.1152/ajpendo.00492.2015 PATTERSON R E, KALAVALAPALLI S, WILLIAMS C M, et al . Lipotoxicity in steatohepatitis occurs despite an increase in tricarboxylic acid cycle activity[J ] . Am J Physiol Endocrinol Metab, 2016, 310(7): E484-E494. DOI: 10.1152/ajpendo.00492.2015.

SUNNY N E BRIL F CUSI K Mitochondrial adaptation in nonalcoholic fatty liver disease: novel mechanisms and treatment strategies Trends Endocrinol Metab 2016 28 4 250 260 10.1016/j.tem.2016.11.006 SUNNY N E, BRIL F, CUSI K. Mitochondrial adaptation in nonalcoholic fatty liver disease: novel mechanisms and treatment strategies[J]. Trends Endocrinol Metab, 2016, 28(4): 250-260. DOI: 10.1016/j.tem.2016.11.006.

BOZAYKUT P SAHIN A KARADEMIR B Endoplasmic reticulum stress related molecular mechanisms in nonalcoholic steatohepatitis Mech Ageing Dev 2016 157 17 29 10.1016/j.mad.2016.07.001 BOZAYKUT P, SAHIN A, KARADEMIR B, et al . Endoplasmic reticulum stress related molecular mechanisms in nonalcoholic steatohepatitis[J ] . Mech Ageing Dev, 2016, 157: 17-29. DOI: 10.1016/j.mad.2016.07.001.

KIRPICH I A MARSANO L S MCCLAIN C J Gut-liver axis, nutrition, and non-alcoholic fatty liver disease Clin Biochem 2015 48 13/14 923 930 http://www.ncbi.nlm.nih.gov/pubmed/26151226 KIRPICH I A, MARSANO L S, MCCLAIN C J. Gut-liver axis, nutrition, and non-alcoholic fatty liver disease[J]. Clin Biochem, 2015, 48(13/14): 923-930. DOI: 0.1016/j.clinbiochem.2015.06.023.

LEAMY A K EGNATCHIK R A SHIOTA M Enhanced synthesis of saturated phospholipids is associated with ER stress and lipotoxicity in palmitate treated hepatic cells J Lipid Res 2014 55 7 1478 1488 10.1194/jlr.M050237 LEAMY A K, EGNATCHIK R A, SHIOTA M, et al . Enhanced synthesis of saturated phospholipids is associated with ER stress and lipotoxicity in palmitate treated hepatic cells[J ] . J Lipid Res, 2014, 55(7): 1478-1488. DOI: 10.1194/jlr.M050237.

DOWMAN J K TOMLINSON J W Newsome P N Pathogenesis of non-alcoholic fatty liver disease QJM 2010 103 2 71 83 10.1093/qjmed/hcp158 DOWMAN J K, TOMLINSON J W, Newsome P N. Pathogenesis of non-alcoholic fatty liver disease[J]. QJM, 2010, 103(2): 71-83. DOI: 10.1093/qjmed/hcp158.

TSUKAMOTO H RIPPE R NIEMELA O Roles of oxidative stress in activation of Kupffer and Ito cells in liver fibrogenesis J Gastroenterol Hepatol 1995 10 Suppl 1 S50 S53 http://www.ncbi.nlm.nih.gov/pubmed/8589343 TSUKAMOTO H, RIPPE R, NIEMELA O, et al . Roles of oxidative stress in activation of Kupffer and Ito cells in liver fibrogenesis[J ] . J Gastroenterol Hepatol, 1995, 10(Suppl 1): S50-S53.

TILG H DIEHL A M Cytokines in alcoholic and nonalcoholic steatohepatitis N Engl J Med 2000 343 20 1467 1476 10.1056/NEJM200011163432007 TILG H, DIEHL A M. Cytokines in alcoholic and nonalcoholic steatohepatitis[J]. N Engl J Med, 2000, 343(20): 1467-1476. DOI: 10.1056/NEJM200011163432007.

LEMMERS A MORENO C GUSTOT T The interleukin-17 pathway is involved in human alcoholic liver disease Hepatology 2009 49 2 646 657 10.1002/hep.22680 LEMMERS A, MORENO C, GUSTOT T, et al . The interleukin-17 pathway is involved in human alcoholic liver disease[J ] . Hepatology, 2009, 49(2): 646-657. DOI: 10.1002/hep.22680.

WEAVER C T HARRINGTON L E MANGAN P R Th17: an effector CD4 T cell lineage with regulatory T cell ties Immunity 2006 24 6 677 688 10.1016/j.immuni.2006.06.002 WEAVER C T, HARRINGTON L E, MANGAN P R, et al . Th17: an effector CD4 T cell lineage with regulatory T cell ties[J ] . Immunity, 2006, 24(6): 677-688. DOI: 10.1016/j.immuni.2006.06.002.

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