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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
October 2014 Volume 10 Issue 4

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
October 2014 Volume 10 Issue 4

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

Inhibition of the interleukin‑23/interleukin‑17 pathway by anti‑interleukin‑23p19 monoclonal antibody attenuates 2,4,6‑trinitrobenzene sulfonic acid‑induced Crohn's disease in rats

  • Authors:
    • Jia Yin Yao
    • Yi Lu
    • Min Zhi
    • Chu Jun Li
    • Pin Jin Hu
    • Xiang Gao
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510655, P.R. China, Department of Anesthesiology, Guangzhou Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong 510130, P.R. China
  • Pages: 2105-2110
    |
    Published online on: July 28, 2014
       https://doi.org/10.3892/mmr.2014.2427
  • 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

The interleukin (IL)‑23/IL‑17 pathway is considered to be important in the pathogenesis of Crohn's disease (CD). The present study aimed to evaluate the effects of targeting the IL‑23/IL‑17 pathway using the anti‑IL‑23p19 monoclonal antibody (mAb) on 2,4,6‑trinitrobenzene sulfonic acid (TNBS)‑induced CD rats. A total of 60 Sprague‑Dawley rats were randomly divided into a control group, model group and an anti‑IL‑23p19 mAb treatment group (administered intramuscularly every week at a dose of 1 ml/mg). Disease activity index (DAI), colon macroscopic damage index (CMDI) and tissue damage index (TDI) were then evaluated. The mRNA expression of IL‑23p19, p40 (IL‑23/12), retinoic acid‑related orphan receptor‑γt (ROR‑γt) and IL‑17 in colonic tissues were detected by reverse transcription‑polymerase chain reaction and levels of serum IL‑23p19, p40, ROR‑γt and IL‑17 were measured using an enzyme‑linked immunosorbent assay. Anti‑IL‑23p19 mAb was found to effectively attenuate colonic inflammation demonstrated by reduced DAI, CMDI and TDI scores, improvement in pathological evaluation and downregulation of expression levels of IL‑23p19, p40 (IL‑23/12), ROR‑γt and the downstream proinflammatory cytokine, IL‑17. Anti‑IL‑23p19 mAb attenuated TNBS‑induced CD in model rats. The possible underlying mechanisms may be associated with inhibition of the IL‑23/IL‑17 pathway by inhibiting the expression of IL‑23p19 and downregulating the downstream proinflammatory cytokine IL‑17. Targeting the IL‑23/IL‑17 pathway may be a relevant and realistic therapeutic approach for the development of additive and alternative treatments to the biologics currently available in the treatment of CD.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Geremia A, Biancheri P, Allan P, Corazza GR and Di Sabatino A: Innate and adaptive immunity in inflammatory bowel disease. Autoimmun Rev. 13:3–10. 2013. View Article : Google Scholar

2 

Oppmann B, Lesley R, Blom B, et al: Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity. 13:715–725. 2000. View Article : Google Scholar

3 

Cua DJ, Sherlock J, Chen Y, et al: Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature. 421:744–748. 2003. View Article : Google Scholar : PubMed/NCBI

4 

Vignali DA and Kuchroo VK: IL-12 family cytokines: immunological playmakers. Nat Immunol. 13:722–728. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Duvallet E, Semerano L, Assier E, Falgarone G and Boissier MC: Interleukin-23: a key cytokine in inflammatory diseases. Ann Med. 43:503–511. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Duerr RH, Taylor KD, Brant SR, et al: A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 314:1461–1463. 2006. View Article : Google Scholar : PubMed/NCBI

7 

McGeachy MJ, Chen Y, Tato CM, et al: The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat Immunol. 10:314–324. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Rovedatti L, Kudo T, Biancheri P, et al: Differential regulation of interleukin 17 and interferon gamma production in inflammatory bowel disease. Gut. 58:1629–1636. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Sarra M, Pallone F, Macdonald TT and Monteleone G: IL-23/IL-17 axis in IBD. Inflamm Bowel Dis. 16:1808–1813. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Siakavellas SI and Bamias G: Role of the IL-23/IL-17 axis in Crohn’s disease. Discov Med. 14:253–262. 2012.

11 

Toussirot E: The IL23/Th17 pathway as a therapeutic target in chronic inflammatory diseases. Inflamm Allergy Drug Targets. 1:159–168. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Imaeda H, Takahashi K, Fujimoto T, et al: Clinical utility of newly developed immunoassays for serum concentrations of adalimumab and anti-adalimumab antibodies in patients with Crohn’s disease. J Gastroenterol. 49:100–109. 2014.PubMed/NCBI

13 

Peyrin-Biroulet L and Danese S: Stopping infliximab in Crohn’s disease: still an ongoing STORI. Inflamm Bowel Dis. 18:2201–2202. 2012.

14 

Kilkenny C, Browne WJ, Cuthill IC, Emerson M and Altman DG: Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 8:e10004122010. View Article : Google Scholar : PubMed/NCBI

15 

Morris GP, Beck PL, Herridge MS, et al: Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology. 96:795–803. 1989.PubMed/NCBI

16 

Murthy SN, Cooper HS, Shim H, Shah RS, Ibrahim SA and Sedergran DJ: Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporin. Dig Dis Sci. 38:1722–1734. 1993. View Article : Google Scholar : PubMed/NCBI

17 

Murano M, Maemura K, Hirata I, et al: Therapeutic effect of intracolonically administered nuclear factor kappa B (p65) antisense oligonucleotide on mouse dextran sulphate sodium (DSS)-induced colitis. Clin Exp Immunol. 120:51–58. 2000. View Article : Google Scholar

18 

Wallace JL and Keenan CM: An orally active inhibitor of leukotriene synthesis accelerates healing in a rat model of colitis. Am J Physiol. 258:G527–G534. 1990.PubMed/NCBI

19 

Guo L, Ye C, Hao X, et al: Carboxyamidotriazole ameliorates experimental colitis by inhibition of cytokine production, nuclear factor-κB activation, and colonic fibrosis. J Pharmacol Exp Ther. 342:356–365. 2012.PubMed/NCBI

20 

Zingarelli B, Hake PW, Burroughs TJ, Piraino G, O’Connor M and Denenberg A: Activator protein-1 signalling pathway and apoptosis are modulated by poly(ADP-ribose) polymerase-1 in experimental colitis. Immunology. 113:509–517. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Neurath MF, Fuss I, Kelsall BL, Stüber E and Strober W: Antibodies to interleukin 12 abrogate established experimental colitis in mice. J Exp Med. 182:1281–1290. 1995. View Article : Google Scholar : PubMed/NCBI

22 

Strober W, Lúdvíksson BR and Fuss IJ: The pathogenesis of mucosal inflammation in murine models of inflammatory bowel disease and Crohn disease. Ann Intern Med. 128:848–856. 1998. View Article : Google Scholar : PubMed/NCBI

23 

Torres MI, Garcia-Martin M, Fernandez MI, Nieto N, Gil A and Rios A: Experimental colitis induced by trinitrobenzenesulfonic acid: an ultrastructural and histochemical study. Dig Dis Sci. 44:2523–2529. 1999. View Article : Google Scholar : PubMed/NCBI

24 

Lakatos PL and Lakatos L: Ulcerative proctitis: a review of pharmacotherapy and management. Expert Opin Pharmacother. 9:741–749. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Burger D and Travis S: Conventional medical management of inflammatory bowel disease. Gastroenterology. 140:1827–1837. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Magro F and Portela F: Management of inflammatory bowel disease with infliximab and other anti-tumor necrosis factor alpha therapies. BioDrugs. 24:3–14. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Mariette X, Matucci-Cerinic M, Pavelka K, et al: Malignancies associated with tumour necrosis factor inhibitors in registries and prospective observational studies: a systematic review and meta-analysis. Ann Rheum Dis. 70:1895–1904. 2011. View Article : Google Scholar

28 

Deepak P, Sifuentes H, Sherid M, Stobaugh D, Sadozai Y and Ehrenpreis ED: T-cell non-Hodgkin’s lymphomas reported to the FDA AERS with tumor necrosis factor-alpha (TNF-α) inhibitors: results of the REFURBISH study. Am J Gastroenterol. 108:99–105. 2013.

29 

Huang R, Valerian BT and Lee EC: Laparoscopic approach in patients with recurrent Crohn’s disease. Am Surg. 78:595–599. 2012.

30 

Ivanov II, McKenzie BS, Zhou L, et al: The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 126:1121–1133. 2006. View Article : Google Scholar : PubMed/NCBI

31 

Ono Y, Kanai T, Sujino T, et al: T-helper 17 and interleukin-17-producing lymphoid tissue inducer-like cells make different contributions to colitis in mice. Gastroenterology. 143:1288–1297. 2012. View Article : Google Scholar : PubMed/NCBI

32 

Guan Q, Ma Y, Hillman CL, et al: Targeting IL-12/IL-23 by employing a p40 peptide-based vaccine ameliorates TNBS-induced acute and chronic murine colitis. Mol Med. 17:646–656. 2011. View Article : Google Scholar : PubMed/NCBI

33 

De Nitto D, Sarra M, Cupi ML, Pallone F and Monteleone G: Targeting IL-23 and Th17-cytokines in inflammatory bowel diseases. Curr Pharm Des. 16:3656–3660. 2010.PubMed/NCBI

34 

Monteleone I, Pallone F and Monteleone G: Interleukin-23 and Th17 cells in the control of gut inflammation. Mediators Inflamm. 2009:2976452009. View Article : Google Scholar : PubMed/NCBI

35 

Cho JH and Brant SR: Recent insights into the genetics of inflammatory bowel disease. Gastroenterology. 140:1704–1712. 2011. View Article : Google Scholar : PubMed/NCBI

36 

Kurzeja M, Rudnicka L and Olszewska M: New interleukin-23 pathway inhibitors in dermatology: ustekinumab, briakinumab and secukinumab. Am J Clin Dermatol. 12:113–125. 2011. View Article : Google Scholar : PubMed/NCBI

37 

Tzellos T, Kyrgidis A, Trigoni A and Zouboulis CC: Association of ustekinumab and briakinumab with major adverse cardiovascular events: An appraisal of meta-analyses and industry sponsored pooled analyses to date. Dermatoendocrinol. 4:320–323. 2012. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yao JY, Lu Y, Zhi M, Li CJ, Hu PJ and Gao X: Inhibition of the interleukin‑23/interleukin‑17 pathway by anti‑interleukin‑23p19 monoclonal antibody attenuates 2,4,6‑trinitrobenzene sulfonic acid‑induced Crohn's disease in rats. Mol Med Rep 10: 2105-2110, 2014.
APA
Yao, J.Y., Lu, Y., Zhi, M., Li, C.J., Hu, P.J., & Gao, X. (2014). Inhibition of the interleukin‑23/interleukin‑17 pathway by anti‑interleukin‑23p19 monoclonal antibody attenuates 2,4,6‑trinitrobenzene sulfonic acid‑induced Crohn's disease in rats. Molecular Medicine Reports, 10, 2105-2110. https://doi.org/10.3892/mmr.2014.2427
MLA
Yao, J. Y., Lu, Y., Zhi, M., Li, C. J., Hu, P. J., Gao, X."Inhibition of the interleukin‑23/interleukin‑17 pathway by anti‑interleukin‑23p19 monoclonal antibody attenuates 2,4,6‑trinitrobenzene sulfonic acid‑induced Crohn's disease in rats". Molecular Medicine Reports 10.4 (2014): 2105-2110.
Chicago
Yao, J. Y., Lu, Y., Zhi, M., Li, C. J., Hu, P. J., Gao, X."Inhibition of the interleukin‑23/interleukin‑17 pathway by anti‑interleukin‑23p19 monoclonal antibody attenuates 2,4,6‑trinitrobenzene sulfonic acid‑induced Crohn's disease in rats". Molecular Medicine Reports 10, no. 4 (2014): 2105-2110. https://doi.org/10.3892/mmr.2014.2427
Copy and paste a formatted citation
x
Spandidos Publications style
Yao JY, Lu Y, Zhi M, Li CJ, Hu PJ and Gao X: Inhibition of the interleukin‑23/interleukin‑17 pathway by anti‑interleukin‑23p19 monoclonal antibody attenuates 2,4,6‑trinitrobenzene sulfonic acid‑induced Crohn's disease in rats. Mol Med Rep 10: 2105-2110, 2014.
APA
Yao, J.Y., Lu, Y., Zhi, M., Li, C.J., Hu, P.J., & Gao, X. (2014). Inhibition of the interleukin‑23/interleukin‑17 pathway by anti‑interleukin‑23p19 monoclonal antibody attenuates 2,4,6‑trinitrobenzene sulfonic acid‑induced Crohn's disease in rats. Molecular Medicine Reports, 10, 2105-2110. https://doi.org/10.3892/mmr.2014.2427
MLA
Yao, J. Y., Lu, Y., Zhi, M., Li, C. J., Hu, P. J., Gao, X."Inhibition of the interleukin‑23/interleukin‑17 pathway by anti‑interleukin‑23p19 monoclonal antibody attenuates 2,4,6‑trinitrobenzene sulfonic acid‑induced Crohn's disease in rats". Molecular Medicine Reports 10.4 (2014): 2105-2110.
Chicago
Yao, J. Y., Lu, Y., Zhi, M., Li, C. J., Hu, P. J., Gao, X."Inhibition of the interleukin‑23/interleukin‑17 pathway by anti‑interleukin‑23p19 monoclonal antibody attenuates 2,4,6‑trinitrobenzene sulfonic acid‑induced Crohn's disease in rats". Molecular Medicine Reports 10, no. 4 (2014): 2105-2110. https://doi.org/10.3892/mmr.2014.2427
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