Open Access Article

International Journal of Clinical Research. 2022; 6: (8) ; 22-27 ; DOI: 10.12208/j.ijcr.20220423.

Research advances of IL-32 in liver disease

作者: 童瑶, 张晓珣, 柴进 *

重庆大学医学院 重庆 ;
陆军军医大学第一附属医院(西南医院)消化内科、全军消化病研究所、胆汁淤积肝病中心、代谢相关性脂肪肝中心 重庆

*通讯作者: 柴进,单位:重庆大学医学院 重庆 ;陆军军医大学第一附属医院(西南医院)消化内科、全军消化病研究所、胆汁淤积肝病中心、代谢相关性脂肪肝中心 重庆;

发布时间: 2022-09-26 总浏览量: 341


白介素32(Interleukin32, IL-32)是一种新型细胞因子,在不同细胞类型中均有表达,可通过经典的促炎细胞因子信号通路诱导炎症的发生,同时也具有调节抗炎细胞因子和免疫抑制分子产生的作用,参与了炎症、肿瘤、肝脏疾病等多种疾病的发生发展。IL-32不同亚型在多种肝脏疾病中起作用,包括肝炎病毒感染、胆汁淤积性肝病、酒精性或非酒精性肝病和肝细胞癌等。本文介绍了IL-32在肝脏疾病中的研究进展,对其在不同肝病中的生物学功能进行初步探讨,也为不同类型的肝脏疾病发病机制及防治策略的研究提供了新的思路。

关键词: 白介素32;肝脏疾病;炎症


Interleukin32 (IL-32) is a novel cytokine, which is expressed in different kinds of cells. IL-32 can induce inflammation through the classical pro-inflammatory cytokine signaling pathway, and also regulates the production of anti-inflammatory cytokines and immunosuppressive molecules. IL-32 is involved in the occurrence and development of inflammation, tumor and other diseases. Different subtypes of IL-32 play a role in a variety of liver diseases, including hepatitis virus infection, cholestatic liver disease, alcoholic or non-alcoholic liver disease, and hepatocellular carcinoma.  In this paper, the research progress of IL-32 in liver diseases was introduced, and its biological functions in different liver diseases were preliminarily discussed, which also provided new ideas for the study of the pathogenesis and prevention strategies.

Key words: Interleukin 32; Liver disease; Inflammation

参考文献 References

[1] KIM S H, HAN S Y, AZAM T, et al.Interleukin-32: a cytokine and inducer of TNFalpha[J]. Immunity, 2005, 22: 131-142.

[2] NISHIMOTO K P, LAUST A K, NELSON E L.A human dendritic cell subset receptive to the Venezuelan equine encephalitis virus-derived replicon particle constitutively expresses IL-32[J]. J Immunol, 2008, 181: 4010-4018.

[3] HEINHUIS B, KOENDERS M I, VAN DEN BERG W B, et al.Interleukin 32 (IL-32) contains a typical alpha-helix bundle structure that resembles focal adhesion targeting region of focal adhesion kinase-1[J]. J Biol Chem, 2012, 287: 5733-5743.

[4] JAEKAL J, JHUN H, HONG J, et al.Cloning and characterization of bovine interleukin-32 beta isoform [J]. Vet Immunol Immunopathol, 2010, 137: 166-171.

[5] SHODA H, FUJIO K, YAMAGUCHI Y, et al.Interactions between IL-32 and tumor necrosis factor alpha contribute to the exacerbation of immune-inflammatory diseases [J]. Arthritis Res Ther, 2006, 8: R166.

[6] MEGUMI KUDO,EMIKO OGAWA D K, AKANE HARUNA, et al.Oxidative stress induced Interleukin-32 mRNA expression in human bronchial epithelial cells[J]. Respiratory Research, 2012, 13(1), 19. 

[7] NETEA M G, AZAM T, LEWIS E C, et al.Mycobacterium tuberculosis induces interleukin-32 production through a caspase- 1/IL-18/interferon- gamma- dependent mechanism[J]. PLoS Med, 2006, 3: e277.

[8] KANG J W, CHOI S C, CHO M C, et al. A proinflammatory cytokine interleukin-32beta promotes the production of an anti-inflammatory cytokine interleukin-10 [J]. Immunology, 2009, 128: e532-540.

[9] SMITH A J, TOLEDO C M, WIETGREFE S W, et al.The immunosuppressive role of IL-32 in lymphatic tissue during HIV-1 infection [J]. J Immunol, 2011, 186: 6576-6584.

[10] HASEGAWA H, THOMAS H J, SCHOOLEY K, et al.Native IL-32 is released from intestinal epithelial cells via a non-classical secretory pathway as a membrane- associated protein [J]. Cytokine, 2011, 53: 74-83.

[11] CHEN Q, CARROLL H P, GADINA M.The Newest Interleukins: Recent Additions to the Ever‐Growing Cytokine Family[M].Vitamins and hormones, 2006, 74, 207–228.

[12] GODA C, KANAJI T, KANAJI S, et al.Involvement of IL-32 in activation-induced cell death in T cells[J]. Int Immunol , 2006, 18: 233-240.

[13] AASS K R, KASTNES M H, STANDAL T. Molecular interactions and functions of IL-32[J]. J Leukoc Biol, 2021, 109: 143-159.

[14] NAKAYAMA M, NIKI Y, KAWASAKI T, et al.IL-32-PAR2 axis is an innate immunity sensor providing alternative signaling for LPS-TRIF axis [J]. Sci Rep, 2013, 3: 2960.

[15] DANIELA NOVICK, MENACHEM RUBINSTEIN, TANIA AZAM, et al. Proteinase 3 is an IL-32 binding protein [J]. Proceedings of the National Academy of Sciences of the United States of America, 2005, 103(9), 3316–3321.

[16] ZHANG X, LI L, ZHAO N, et al. A novel role for interleukin 32 in cholestasis[J]. Clin Transl Med, 2021, 11: e594.

[17] OKAMURA A, HARADA K, NIO M, et al.Interleukin-32 production associated with biliary innate immunity and proinflammatory cytokines contributes to the pathogenesis of cholangitis in biliary atresia[J]. Clin Exp Immunol, 2013, 173: 268-275.

[18] ZHANG J, LUO Y, FENG M, et al.Identification of Liver Immune Microenvironment-Related Hub Genes in Liver of Biliary Atresia[J].Frontiers in pediatrics, 2022, 9, 786422.

[19] XU Z, DONG A, FENG Z, et al. Interleukin-32 promotes lipid accumulation through inhibition of cholesterol efflux. Exp Ther Med [J], 2017, 14: 947-952.

[20] DAMEN M, DOS SANTOS J C, HERMSEN R, et al.Interleukin-32 upregulates the expression of ABCA1 and ABCG1 resulting in reduced intracellular lipid concentrations in primary human hepatocytes[J]. Atherosclerosis, 2018, 271: 193-202.

[21] CATALáN V. Increased Interleukin-32 Levels in Obesity Promote Adipose Tissue Inflammation and Extracellular Matrix Remodeling: Effect of Weight Loss[J]. diabetes, 2016, 65(12), 3636–3648.

[22] DALI-YOUCEF N, VIX M, COSTANTINO F, et al.Interleukin-32 Contributes to Human Nonalcoholic Fatty Liver Disease and Insulin Resistance[J]. Hepatol Commun, 2019, 3: 1205-1220.

[23] BASELLI G A, DONGIOVANNI P, RAMETTA R, et al.Liver transcriptomics highlights interleukin-32 as novel NAFLD-related cytokine and candidate biomarker[J]. Gut, 2020, 69: 1855-1866.

[24] DALI-YOUCEF N, MECILI M, RICCI R, et al.Metabolic inflammation: connecting obesity and insulin resistance[J]. Ann Med, 2013, 45: 242-253.

[25] LEE D H, KIM D H, HWANG C J, et al.Interleukin-32gamma attenuates ethanol-induced liver injury by the inhibition of cytochrome P450 2E1 expression and inflammatory responses [J]. Clin Sci (Lond), 2015, 128: 695-706.

[26] KOURKOUMPETIS T, SOOD G. Pathogenesis of Alcoholic Liver Disease: An Update [J]. Clin Liver Dis, 2019, 23: 71-80.

[27] PAN X, CAO H, LU J, et al.Interleukin-32 expression induced by hepatitis B virus protein X is mediated through activation of NF-kappaB [J]. Mol Immunol, 2011, 48: 1573-1577.

[28] ZOU Y, BAO J, PAN X, et al.NKP30-B7-H6 Interaction Aggravates Hepatocyte Damage through Up-Regulation of Interleukin-32 Expression in Hepatitis B Virus-Related Acute-On-Chronic Liver Failure[J]. PLoS One , 2015, 10: e0134568.

[29] TIAN Z J, SHEN Y, LI X R, et al.Increased interleukin-32, interleukin-1, and interferon-gamma levels in serum from hepatitis B patients and in HBV-stimulated peripheral blood mononuclear cells from healthy volunteers. J Infect Public Health [J], 2019, 12: 7-12.

[30] KIM D H, PARK E S, LEE A R, et al. Intracellular interleukin-32gamma mediates antiviral activity of cytokines against hepatitis B virus [J]. Nat Commun, 2018, 9: 3284.

[31] MOSCHEN A R, FRITZ T, CLOUSTON A D, et al. Interleukin-32: a new proinflammatory cytokine involved in hepatitis C virus-related liver inflammation and fibrosis[J]. Hepatology,  2011, 53: 1819-1829.

[32] LIU B, MA X, WANG Q, et al.Marmoset Viral Hepatic Inflammation Induced by Hepatitis C Virus Core Protein via IL-32 [J]. Front Cell Infect Microbiol, 2020, 10: 135.

[33] KO N Y, CHANG S H, LEE J H, et al. Unique expression of a small IL-32 protein in the Jurkat leukemic T cell line[J]. Cytokine, 2008, 42: 121-127.

[34] KANG Y H, PARK M Y, YOON D Y, et al.Dysregulation of overexpressed IL-32alpha in hepatocellular carcinoma suppresses cell growth and induces apoptosis through inactivation of NF-kappaB and Bcl-2[J]. Cancer Lett, 2012, 318: 226-233.


童瑶, 张晓珣, 柴进, 细胞因子IL-32在肝脏疾病中的研究进展[J]. 国际临床研究杂志, 2022; 6: (8) : 22-27.