Mechanism of action of 1,25(OH)_2D_3 in influencing the expression of interleukin-17 and macrophage inflammatory protein-3α and inhibiting the formation of liver fibrosis in rats

Li XiaoTian; Yin Yan; Guo YongZe; Zhou LiYun; You ZiXuan

doi:10.3969/j.issn.1001-5256.2016.12.020

Issue 12

Dec. 2016

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Article Navigation > Journal of Clinical Hepatology > 2016 > 32(12): 2331-2336

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Mechanism of action of 1,25(OH)_2D_3 in influencing the expression of interleukin-17 and macrophage inflammatory protein-3α and inhibiting the formation of liver fibrosis in rats

DOI: 10.3969/j.issn.1001-5256.2016.12.020

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Published Date: 2016-12-20

Abstract

Abstract

Objective To investigate the changes in the expression of interleukin- 17( IL- 17) and macrophage inflammatory protein- 3α( MIP- 3α) in liver tissue and peripheral blood during the formation of liver fibrosis and the mechanism of action of 1,25( OH)2D3in influencing the IL- 17 pathway and inhibiting the formation of liver fibrosis. Methods A total of 48 Sprague- Dawley rats were randomly divided into normal group( olive oil),model group( CCl4 olive oil solution),drug control group( CCl4 olive oil solution + olive oil by gavage),and treatment group( CCl4 olive oil solution + 1,25( OH)2D3olive oil solution by gavage). Eight weeks later the liver tissue was collected for HE staining and Masson staining to determine the pathological staging of fibrosis. ELISA was used to measure the serum level of IL- 17 at different time points after intervention( weeks 4,6,and 8). Immunohistochemistry was used to measure the protein expression of IL- 17 and MIP- 3α in liver tissue at different time points( weeks 4,6,and 8),and real time- PCR was used to measure the mRNA expression of IL- 17 and MIP- 3α in liver tissue at week 8 after intervention. A one- way analysis of variance was used for comparison of continuous data between groups,and the LSD- t test was used for further pairwise comparison. The linear regression analysis was used for correlation analysis. Results At week 8 after intervention,the model group and the drug control group had significant liver fibrosis,and the treatment group had significant alleviation in liver fibrosis. There were significant differences in serum IL- 17 level between the four groups at weeks4,6,and 8( F = 6. 13,5. 79,and 7. 18,all P < 0. 05). The normal group had an extremely low serum level of IL- 17; at each time point,the model group and the drug control group had a significant increase in the serum level of IL- 17 compared with the normal group( all P < 0. 01). At each time point,the treamtent group had significant reductions in the serum level of IL- 17 compared with the model group and the drug control group( all P < 0. 05),and all the groups had the highest level at week 4. Immunohistochemistry and real time-PCR showed that there was almost no expression of IL- 17 and a very low expression level of MIP- 3α in liver tissue in the control group.With the progression of liver fibrosis,serum IL- 17 level decreased gradually,while the IL- 17 level in liver tissue increased gradually( r=- 0. 793,P < 0. 01). There were significant differences in the expression of IL- 17 and MIP- 3α in liver tissue between the four groups at weeks 4,6,and 8( IL- 17: F = 11. 02,9. 61,and 7. 45,all P < 0. 05; MIP- 3α: F = 9. 47,8. 93,and 6. 15,all P < 0. 05). The model group and the drug control group had significant increases in the protein expression of IL- 17 and MIP- 3α in liver tissue compared with the normal group at weeks 4,6,and 8( all P < 0. 01),and the treatment group had significant reductions compared with the drug control group at these time points( all P < 0. 05); all the groups had the highest expression at week 8. At week 8,the model group and the drug control group had significant increases in the mRNA expression of IL- 17 and MIP- 3α compared with the normal group,and the treatment group had significant reductions compared with the drug control group and the model group( FIL- 17= 7. 36,FMIP- 3α= 10. 15,both P < 0.05). Conclusion During the development and progression of liver fibrosis,serum IL- 17 level first increases and then decreases,while the expression of IL- 17 in liver tissue tends to increase gradually,suggesting that in the late stage of liver fibrosis,Th17 cells in serum tend to accumulate in the liver. The 1,25( OH)2D3treatment group had significant reductions in the protein and mRNA expression of IL- 17 and MIP- 3α in the liver compared with the model group and the drug control group,suggesting that the IL- 17 pathway may be one mechanism of action of 1,25( OH)2D3in inhibiting the development and progression of liver fibrosis.
- liver cirrhosis,
- interleukin-17,
- macrophage inflammatory proteins,
- calcitriol,
- rats,Sprague-Dawley

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References(17)

References

[1]FU LZ,ZHENG T,ZHANG YS.Advances in understanding the role of TGF-β/Smad signalling pathways in the pathogenesis of liver fibrosis[J].Chin J Clin Pharmacol Ther,2014,19(10):1189-1195.(in Chinese)付玲珠,郑婷,张永生.TGF-β/Smad信号转导通路与肝纤维化研究进展[J].中国临床药理学与治疗学,2014,19(10):1189-1195.

[2]LU LG,LI ZH.Recent research on liver fibrosis and cirrhosis[J].J Clin Hepatol,2013,29(5):321-323.(in Chinese)陆伦根,李郑红.肝纤维化及肝硬化研究近况[J].临床肝胆病杂志,2013,29(5):321-323.

[3]LI YF,TANG XL,LING WH.1,25-dihydroxyvitamin D3 inhibits fi brosis in mice with NAFLD induced by a methioninecholinedeficient diet[J].World Chin J Dig,2012,20(33):3191-3198.(in Chinese)李艳芳,唐夕岚,凌文华.1,25-二羟基维生素D3对小鼠非酒精性脂肪肝性肝纤维化进程的抑制作用[J].世界华人消化杂志,2012,20(33):3191-3198.

[4]YIN Y,YU ZW,XIA M,et al.Vitamin D attenuates high fat diet-induced hepatic steatosis in rats by modulating lipid metabolism[J].Eur J Clin invest,2012,42(11):1189-1196.

[5]KITSON MT,SARRAZIN C,TONIUTTO P,et al.Vitamin D level and sustained virologic response to interferon-based anti-viral therapy in chronic hepatitis C:a systematic review and meta-analysis[J].J Hepatol,2014,61(6):1247-1252.

[6]GUELI N,VERRUSIO W,LINGUANTI A,et al.Vitamin D:drug of the future.A new therapeutic approach[J].Arch Gerontol Geriat,2012,54(1):222-227.

[7]WU Q,MENG FP,MA XM,et al.Analysis of association between different HCV genotypes and serum interleukin-17,interleukin-6,and vitamin D in patients with HCV-related cirrhosis[J].J Clin Hepatol,2015,31(11):1849-1852.(in Chinese)吴勤,孟繁平,马雪梅,等.丙型肝炎肝硬化患者HCV基因型与血清白细胞介素17、白细胞介素6及维生素D的关系[J].临床肝胆病杂志,2015,31(11):1849-1852.

[8]ZENG MD,WANG TL,WANG BE.Consensus on diagnosis and therapeutic effect evaluation of hepatic fibrosis[J].Chin Hepatol,2002,7(2):s3-s4.(in Chinese)曾民德,王泰龄,王宝恩.肝纤维化诊断及疗效评估共识[J].肝脏,2002,7(2):s3-s4.

[9]WANG TL,LIU X,GAO L,et al.Classification,grading,and staging of chronic hepatitis[J].Chin J Hepatol,1995,2(3):130-136.(in Chinese)王泰龄,刘霞,高琳,等.对慢性肝炎分类、分级分期的探讨[J].中华肝脏病杂志,1995,2(3):130-136.

[10]GU L,DENG WS,SUN XF,et al.Rapamycin ameliorates CCl4-induced liver fibrosis in mice through reciprocal regulation of the Th17/Treg cell balance[J].Mol Med Rep,2016,14(2):1153-1161.

[11]RUTITZKY LI,BAZZONE L,SHAINHEIT MG,et al.IL-23 is required for the development of severe egg-induced immunopathology in schistosomiasis and for lesional expression of IL-17[J].J Immunol,2008,180(4):2486-2495.

[12]MENG F,WANG K,AOYAMA T,et al.Interleukin-17 signaling in inflammatory,Kuffer cells,and hepatic stellate cells exacerbates liver fibrosis in mice[J].Gastroenterology,2012,143(3):765-776.

[13]WANG L,LI XT,ZHANG L,et al.Inhibitory and apoptotic effect of LY 294002in combination with 1,25-dihydroxyvitamin D3 on HSC T6 cells in vitro[J].J Pract Hepatol,2016,19(2):147-150.(in Chinese)王蕾,李校天,张利,等.活性维生素D3联合LY294002体外抑制大鼠肝星状细胞增殖作用研究[J].实用肝脏病杂志,2016,19(2):147-150.

[14]PALMER MT,LEE YK,MAYNARD CL,et al.Lineage-specific effects of 1,25-dihydroxyvitamin D3 on the development of effector CD4 T cells[J].J Biol Chem,2011,286(2):997-1004.

[15]PAINTLIA AS,PAINTLIA MK,HOLLIS BW,et al.Interference with Rho A-ROCK signaling mechanismin autoreactive CD4+T cells enhances the bioavailability of 1,25-dihydroxyvitamin D3 in experimental autoimmune encephalomyelitis[J].Am J Pathol,2012,181(3):993-1006.

[16]TANG J,ZHOU R,LUGER D,et al.Calcitriol supresses antiretinal autoimmunity throungh inhibitory effects on the Th17 effector responsel[J].J Immunol,2009,182(8):4624-4632.

[17]CHANG SH,CHUNG Y,DONG C.Vitamin D supresses Th17 cytokine production by inducing C/EBP homologous protein(CHOP)expression[J].J Biol Chem,2010,285:38751-38755.

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Mechanism of action of 1,25(OH)_2D_3 in influencing the expression of interleukin-17 and macrophage inflammatory protein-3α and inhibiting the formation of liver fibrosis in rats

DOI: 10.3969/j.issn.1001-5256.2016.12.020