Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
June-2021 Volume 21 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
June-2021 Volume 21 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Interleukin-12 exacerbates symptoms in an MRL/MpJ-Faslpr mouse model of systemic lupus erythematosus

  • Authors:
    • Ling Li
    • Xiaojun Sun
    • Sisi Wu
    • Xin Yuan
    • Bingxin Liu
    • Xueping Zhou
  • View Affiliations / Copyright

    Affiliations: Department of Rheumatology, Taizhou Hospital Affiliated to Nanjing University of Chinese Medicine, Taizhou, Jiangsu 225300, P.R. China, Medical Intensive Care Unit, Ningbo Women and Children's Hospital, Ningbo, Zhejiang 315000, P.R. China, Department of Rheumatology, Jiangsu Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China, Institute of Acute Disorders of Traditional Chinese Internal Medicine, The First Clinical College of Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 627
    |
    Published online on: April 15, 2021
       https://doi.org/10.3892/etm.2021.10059
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Interleukin (IL)-12 modulates the generation and function of a variety of immune cells and serves an important role in the pathogenesis of autoimmune diseases. However, the precise role of IL-12 in the pathogenesis of systemic lupus erythematosus (SLE) remains to be elucidated. In the present study, the serum levels of IL-12 in patients with SLE were determined using an ELISA. The association between serum levels of IL-12 and clinical and laboratory indices, specifically, disease activity and complement 3, were analyzed. Recombinant IL-12 or an anti-IL-12 antibody was used to treat the MRL/MpJ-Faslpr mouse model of systemic lupus erythematosus. The glomerulonephritis and inflammatory cell infiltration was examined to evaluate histological changes using hematoxylin and eosin and Periodic acid-Schiff staining. Serum creatinine and proteinuria were used to determine renal function. The levels of anti-double stranded DNA and anti-nuclear autoantibodies were assessed. The results demonstrated that serum levels of IL-12 were markedly increased in patients with SLE compared with controls and in lupus model mice in comparison with control mice. The serum levels of IL-12 increased with disease severity in patients with SLE. SLE-like symptoms were exacerbated in lupus model mice treated with exogenous IL-12. However, SLE-like symptoms were ameliorated in lupus model mice treated with an anti-IL-12 antibody. The present results demonstrated that IL-12 aggravated SLE and anti-IL12 antibodies ameliorated SLE. The present data suggest that blocking IL-12 may be a beneficial therapeutic strategy to halt the progression of lupus nephritis.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Anders HJ, Saxena R, Zhao MH, Parodis I, Salmon JE and Mohan C: Lupus nephritis. Nat Rev Dis Primers. 6(7)2020.PubMed/NCBI View Article : Google Scholar

2 

Stokes MB and D'Agati VD: Classification of lupus nephritis: Time for a change? Adv Chronic Kidney Dis. 26:323–329. 2019.PubMed/NCBI View Article : Google Scholar

3 

Davidson A, Aranow C and Mackay M: Lupus nephritis: Challenges and progress. Curr Opin Rheumatol. 31:682–688. 2019.PubMed/NCBI View Article : Google Scholar

4 

Song K, Liu L, Zhang X and Chen X: An update on genetic susceptibility in lupus nephritis. Clin Immunol. 210(108272)2020.PubMed/NCBI View Article : Google Scholar

5 

Yang X, Yao G, Chen W, Tang X, Feng X and Sun L: Exacerbation of lupus nephritis by high sodium chloride related to activation of SGK1 pathway. Int Immunopharmacol. 29:568–573. 2015.PubMed/NCBI View Article : Google Scholar

6 

Frangou E, Georgakis S and Bertsias G: Update on the cellular and molecular aspects of lupus nephritis. Clin Immunol. 216(108445)2020.PubMed/NCBI View Article : Google Scholar

7 

Tang Y, Zhang W, Zhu M, Zheng L, Xie L, Yao Z, Zhang H, Cao D and Lu B: Lupus nephritis pathology prediction with clinical indices. Sci Rep. 8(10231)2018.PubMed/NCBI View Article : Google Scholar

8 

Trinchieri G: Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol. 3:133–146. 2003.PubMed/NCBI View Article : Google Scholar

9 

Kang BY, Kim E and Kim TS: Regulatory mechanisms and their therapeutic implications of interleukin-12 production in immune cells. Cell Signal. 17:665–673. 2005.PubMed/NCBI View Article : Google Scholar

10 

Ma CS, Suryani S, Avery DT, Chan A, Nanan R, Santner-Nanan B, Deenick EK and Tangye SG: Early commitment of naïve human CD4(+) T cells to the T follicular helper (T(FH)) cell lineage is induced by IL-12. Immunol Cell Biol. 87:590–600. 2009.PubMed/NCBI View Article : Google Scholar

11 

Teng MWL, Bowman EP, McElwee JJ, Smyth MJ, Casanova JL, Cooper AM and Cua DJ: IL-12 and IL-23 cytokines: From discovery to targeted therapies for immune-mediated inflammatory diseases. Nat Med. 21:719–729. 2015.PubMed/NCBI View Article : Google Scholar

12 

Sandborn WJ, Gasink C, Gao LL, Blank MA, Johanns J, Guzzo C, Sands BE, Hanauer SB, Targan S, Rutgeerts P, et al: CERTIFI Study Group: Ustekinumab induction and maintenance therapy in refractory Crohn's disease. N Engl J Med. 367:1519–1528. 2012.PubMed/NCBI View Article : Google Scholar

13 

Vom Berg J, Prokop S, Miller KR, Obst J, Kälin RE, Lopategui-Cabezas I, Wegner A, Mair F, Schipke CG, Peters O, et al: Inhibition of IL-12/IL-23 signaling reduces Alzheimer's disease-like pathology and cognitive decline. Nat Med. 18:1812–1819. 2012.PubMed/NCBI View Article : Google Scholar

14 

Ueno H: The IL-12-STAT4 axis in the pathogenesis of human systemic lupus erythematosus. Eur J Immunol. 50:10–16. 2020.PubMed/NCBI View Article : Google Scholar

15 

Huang X, Hua J, Shen N and Chen S: Dysregulated expression of interleukin-23 and interleukin-12 subunits in systemic lupus erythematosus patients. Mod Rheumatol. 17:220–223. 2007.PubMed/NCBI View Article : Google Scholar

16 

Hochberg MC: Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 40:1725–1726. 1997.PubMed/NCBI View Article : Google Scholar

17 

Weening JJ, D'Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, Balow JE, Bruijn JA, Cook T, Ferrario F, et al: International Society of Nephrology Working Group on the Classification of Lupus Nephritis; Renal Pathology Society Working Group on the Classification of Lupus Nephritis: The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int. 65:521–530. 2004.PubMed/NCBI View Article : Google Scholar

18 

Li W, Titov AA and Morel L: An update on lupus animal models. Curr Opin Rheumatol. 29:434–441. 2017.PubMed/NCBI View Article : Google Scholar

19 

Yao G, Qi J, Zhang Z, Huang S, Geng L, Li W, Chen W, Tang X, Wang S and Sun L: Endothelial cell injury is involved in atherosclerosis and lupus symptoms in gld.apoE-/- mice. Int J Rheum Dis. 22:488–496. 2019.PubMed/NCBI View Article : Google Scholar

20 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-∆ ∆ C(T)) Method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar

21 

Larosa M, Zen M, Gatto M, Jesus D, Zanatta E, Iaccarino L, Inês L and Doria A: IL-12 and IL-23/Th17 axis in systemic lupus erythematosus. Exp Biol Med (Maywood). 244:42–51. 2019.PubMed/NCBI View Article : Google Scholar

22 

Zundler S and Neurath MF: Interleukin-12: Functional activities and implications for disease. Cytokine Growth Factor Rev. 26:559–568. 2015.PubMed/NCBI View Article : Google Scholar

23 

Trembleau S, Penna G, Gregori S, Giarratana N and Adorini L: IL-12 administration accelerates autoimmune diabetes in both wild-type and IFN-gamma-deficient nonobese diabetic mice, revealing pathogenic and protective effects of IL-12-induced IFN-gamma. J Immunol. 170:5491–5501. 2003.PubMed/NCBI View Article : Google Scholar

24 

Smith T, Hewson AK, Kingsley CI, Leonard JP and Cuzner ML: Interleukin-12 induces relapse in experimental allergic encephalomyelitis in the Lewis rat. Am J Pathol. 150:1909–1917. 1997.PubMed/NCBI

25 

Constantinescu CS, Wysocka M, Hilliard B, Ventura ES, Lavi E, Trinchieri G and Rostami A: Antibodies against IL-12 prevent superantigen-induced and spontaneous relapses of experimental autoimmune encephalomyelitis. J Immunol. 161:5097–5104. 1998.PubMed/NCBI

26 

McIntyre KW, Shuster DJ, Gillooly KM, Warrier RR, Connaughton SE, Hall LB, Arp LH, Gately MK and Magram J: Reduced incidence and severity of collagen-induced arthritis in interleukin-12-deficient mice. Eur J Immunol. 26:2933–2938. 1996.PubMed/NCBI View Article : Google Scholar

27 

Malfait AM, Butler DM, Presky DH, Maini RN, Brennan FM and Feldmann M: Blockade of IL-12 during the induction of collagen-induced arthritis (CIA) markedly attenuates the severity of the arthritis. Clin Exp Immunol. 111:377–383. 1998.PubMed/NCBI View Article : Google Scholar

28 

Talaat RM, Mohamed SF, Bassyouni IH and Raouf AA: Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity. Cytokine. 72:146–153. 2015.PubMed/NCBI View Article : Google Scholar

29 

Lauwerys BR, Van Snick J and Houssiau FA: Serum IL-12 in systemic lupus erythematosus: Absence of p70 heterodimers but presence of p40 monomers correlating with disease activity. Lupus. 11:384–387. 2002.PubMed/NCBI View Article : Google Scholar

30 

Segal R, Dayan M, Zinger H, Habut B, Shearer GM and Mozes E: The effect of IL-12 on clinical and laboratory aspects of experimental SLE in young and aging mice. Exp Gerontol. 38:661–668. 2003.PubMed/NCBI View Article : Google Scholar

31 

Neumann D, Tschernig T, Popa D, Schmiedl A, Pérez de Lema G, Resch K and Martin MU: Injection of IL-12- and IL-18-encoding plasmids ameliorates the autoimmune pathology of MRL/Mp-Tnfrsf6lpr mice: Synergistic effect on autoimmune symptoms. Int Immunol. 18:1779–1787. 2006.PubMed/NCBI View Article : Google Scholar

32 

Kikawada E, Lenda DM and Kelley VR: IL-12 deficiency in MRL-Fas(lpr) mice delays nephritis and intrarenal IFN-γ expression, and diminishes systemic pathology. J Immunol. 170:3915–3925. 2003.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li L, Sun X, Wu S, Yuan X, Liu B and Zhou X: Interleukin-12 exacerbates symptoms in an MRL/MpJ-Faslpr mouse model of systemic lupus erythematosus. Exp Ther Med 21: 627, 2021.
APA
Li, L., Sun, X., Wu, S., Yuan, X., Liu, B., & Zhou, X. (2021). Interleukin-12 exacerbates symptoms in an MRL/MpJ-Faslpr mouse model of systemic lupus erythematosus. Experimental and Therapeutic Medicine, 21, 627. https://doi.org/10.3892/etm.2021.10059
MLA
Li, L., Sun, X., Wu, S., Yuan, X., Liu, B., Zhou, X."Interleukin-12 exacerbates symptoms in an MRL/MpJ-Faslpr mouse model of systemic lupus erythematosus". Experimental and Therapeutic Medicine 21.6 (2021): 627.
Chicago
Li, L., Sun, X., Wu, S., Yuan, X., Liu, B., Zhou, X."Interleukin-12 exacerbates symptoms in an MRL/MpJ-Faslpr mouse model of systemic lupus erythematosus". Experimental and Therapeutic Medicine 21, no. 6 (2021): 627. https://doi.org/10.3892/etm.2021.10059
Copy and paste a formatted citation
x
Spandidos Publications style
Li L, Sun X, Wu S, Yuan X, Liu B and Zhou X: Interleukin-12 exacerbates symptoms in an MRL/MpJ-Faslpr mouse model of systemic lupus erythematosus. Exp Ther Med 21: 627, 2021.
APA
Li, L., Sun, X., Wu, S., Yuan, X., Liu, B., & Zhou, X. (2021). Interleukin-12 exacerbates symptoms in an MRL/MpJ-Faslpr mouse model of systemic lupus erythematosus. Experimental and Therapeutic Medicine, 21, 627. https://doi.org/10.3892/etm.2021.10059
MLA
Li, L., Sun, X., Wu, S., Yuan, X., Liu, B., Zhou, X."Interleukin-12 exacerbates symptoms in an MRL/MpJ-Faslpr mouse model of systemic lupus erythematosus". Experimental and Therapeutic Medicine 21.6 (2021): 627.
Chicago
Li, L., Sun, X., Wu, S., Yuan, X., Liu, B., Zhou, X."Interleukin-12 exacerbates symptoms in an MRL/MpJ-Faslpr mouse model of systemic lupus erythematosus". Experimental and Therapeutic Medicine 21, no. 6 (2021): 627. https://doi.org/10.3892/etm.2021.10059
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team