Immune Mechanisms of Concanavalin A Model of Autoimmune Hepatitis

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2012 Jan 19

PMID 22253517

Citations 111

Authors

Hai-Xia Wang

Man Liu

Shun-Yan Weng

Jing-Jing Li

Chao Xie

Hong-Lin He

Wen Guan

Yun-Sheng Yuan

Jin Gao

Affiliations

Soon will be listed here.

Abstract

As a chronic inflammatory disease of the liver, the pathogenic mechanisms of autoimmune hepatitis (AIH) have not yet been elucidated, with prognosis and diagnosis remaining unsatisfied. Currently the only viable treatments of AIH are immunosuppressant application and liver transplantation. It is considered that lack of good animal AIH models is the main reason for the shortage of a simple and efficient cure. The Concanavalin A (Con A) model is a typical and well established model for investigating T-cell and macrophage dependent liver injury in mice, which closely mimics the pathogenesis mechanisms and pathological changes of patients, and is regarded as the best experimental model for AIH research so far. In this paper we elucidated the pathogenic mechanisms of AIH and the evolution of relative animal models. We go on to further focus on Con A-induced liver injury from the point of immunological mechanisms and the change of cytokine levels. Finally, we manifested the clinical significance of the AIH animal models and the challenges they would meet during their future development.

Citing Articles

Macrophage expression of constitutively active alleviates hepatic injury in a mouse model of concanavalin A-induced autoimmune hepatitis.

Pudgerd A, Pluangnooch P, Soontrapa K, Saedan S, Vanichviriyakit R, Sridurongrit S Heliyon. 2025; 11(4):e42691.

PMID: 40040984 PMC: 11876931. DOI: 10.1016/j.heliyon.2025.e42691.

Sappanone A Ameliorates Concanavalin A-induced Immune-Mediated Liver Injury by Regulating M1 Macrophage Polarization.

Yan F, Li W, Sun X, Wang L, Liu Z, Zhong Z Inflammation. 2024; .

PMID: 39589634 DOI: 10.1007/s10753-024-02189-x.

Rhoifolin Attenuates Concanavalin A-Induced Autoimmune Hepatitis in Mice via JAKs/STATs Mediated Immune and Apoptotic Processes.

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PMID: 39464476 PMC: 11500133. DOI: 10.1021/acsomega.4c07915.

Intracellular osteopontin potentiates the immunosuppressive activity of mesenchymal stromal cells.

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Hepatoprotective Effect of Camel Thorn Polyphenols in Concanavalin A-Induced Hepatitis in Mice.

El-Mahdy N, El-Masry T, El-Tarahony A, Alherz F, Osman E Chin J Integr Med. 2024; 30(12):1090-1100.

PMID: 39298072 DOI: 10.1007/s11655-024-3808-3.

References

Nakano T, Goto S, Lai C, Hsu L, Takaoka Y, Kawamoto S . Immunological aspects and therapeutic significance of an autoantibody against histone H1 in a rat model of concanavalin A-induced hepatitis. Immunology. 2010; 129(4):547-55. PMC: 2842501. DOI: 10.1111/j.1365-2567.2009.03149.x. View

Tsukamoto H . Is interleukin-10 antifibrogenic in chronic liver injury?. Hepatology. 1998; 28(6):1707-9. DOI: 10.1002/hep.510280635. View

Kusters S, Gantner F, Kunstle G, Tiegs G . Interferon gamma plays a critical role in T cell-dependent liver injury in mice initiated by concanavalin A. Gastroenterology. 1996; 111(2):462-71. DOI: 10.1053/gast.1996.v111.pm8690213. View

Repellin C, Tsimbouri P, Philbey A, Wilson J . Lymphoid hyperplasia and lymphoma in transgenic mice expressing the small non-coding RNA, EBER1 of Epstein-Barr virus. PLoS One. 2010; 5(2):e9092. PMC: 2817001. DOI: 10.1371/journal.pone.0009092. View

El Hefnawi M, El Behaidy W, Youssif A, Ghalwash A, El Housseiny L, Zada S . Natural genetic engineering of hepatitis C virus NS5A for immune system counterattack. Ann N Y Acad Sci. 2009; 1178:173-85. DOI: 10.1111/j.1749-6632.2009.05003.x. View

Jirillo E, Caccavo D, Magrone T, Piccigallo E, Amati L, Lembo A . The role of the liver in the response to LPS: experimental and clinical findings. J Endotoxin Res. 2003; 8(5):319-27. DOI: 10.1179/096805102125000641. View

Tiegs G, Hentschel J, Wendel A . A T cell-dependent experimental liver injury in mice inducible by concanavalin A. J Clin Invest. 1992; 90(1):196-203. PMC: 443081. DOI: 10.1172/JCI115836. View

Fayad R, Sennello J, Kim S, Pini M, Dinarello C, Fantuzzi G . Induction of thymocyte apoptosis by systemic administration of concanavalin A in mice: role of TNF-alpha, IFN-gamma and glucocorticoids. Eur J Immunol. 2005; 35(8):2304-12. DOI: 10.1002/eji.200526062. View

Czaja A, Menon K, Carpenter H . Sustained remission after corticosteroid therapy for type 1 autoimmune hepatitis: a retrospective analysis. Hepatology. 2002; 35(4):890-7. DOI: 10.1053/jhep.2002.32485. View

10.

Yamashita J, Iwamura C, Sasaki T, Mitsumori K, Ohshima K, Hada K . Apolipoprotein A-II suppressed concanavalin A-induced hepatitis via the inhibition of CD4 T cell function. J Immunol. 2011; 186(6):3410-20. DOI: 10.4049/jimmunol.1002924. View

11.

Soares P, Nascimento C, Porto T, Correia M, Porto A, Carneiro-da-Cunha M . Purification of a lectin from Canavalia ensiformis using PEG-citrate aqueous two-phase system. J Chromatogr B Analyt Technol Biomed Life Sci. 2011; 879(5-6):457-60. DOI: 10.1016/j.jchromb.2010.12.030. View

12.

Longhi M, Hussain M, Kwok W, Mieli-Vergani G, Ma Y, Vergani D . Autoantigen-specific regulatory T cells, a potential tool for immune-tolerance reconstitution in type-2 autoimmune hepatitis. Hepatology. 2011; 53(2):536-47. DOI: 10.1002/hep.24039. View

13.

Lapierre P, Djilali-Saiah I, Vitozzi S, Alvarez F . A murine model of type 2 autoimmune hepatitis: Xenoimmunization with human antigens. Hepatology. 2004; 39(4):1066-74. DOI: 10.1002/hep.20109. View

14.

Zhang X, Wei H, Rui S, Wei H, Tian Z . Opposite effects of high and low doses of interleukin-2 on T cell-mediated hepatitis in mice (interleukin-2 on hepatitis). Hepatol Int. 2010; 4(3):641-8. PMC: 2940003. DOI: 10.1007/s12072-010-9196-0. View

15.

Lohse A, Manns M, Dienes H, Meyer zum Buschenfelde K, Cohen I . Experimental autoimmune hepatitis: disease induction, time course and T-cell reactivity. Hepatology. 1990; 11(1):24-30. DOI: 10.1002/hep.1840110106. View

16.

de Winther M, Heeringa P . Bone marrow transplantations to study gene function in hematopoietic cells. Methods Mol Biol. 2010; 693:309-20. DOI: 10.1007/978-1-60761-974-1_19. View

17.

Thiele G, Duryee M, Willis M, Tuma D, Radio S, Hunter C . Autoimmune hepatitis induced by syngeneic liver cytosolic proteins biotransformed by alcohol metabolites. Alcohol Clin Exp Res. 2010; 34(12):2126-36. PMC: 3014581. DOI: 10.1111/j.1530-0277.2010.01309.x. View

18.

Hunter A, Holscher M, Neal R . Thioacetamide-induced hepatic necrosis. I. Involvement of the mixed-function oxidase enzyme system. J Pharmacol Exp Ther. 1977; 200(2):439-48. View

19.

Varthaman A, Khallou-Laschet J, Clement M, Fornasa G, Kim H, Gaston A . Control of T cell reactivation by regulatory Qa-1-restricted CD8+ T cells. J Immunol. 2010; 184(12):6585-91. DOI: 10.4049/jimmunol.0903109. View

20.

. Final report on carcinogens background document for formaldehyde. Rep Carcinog Backgr Doc. 2010; (10-5981):i-512. View