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Chicken type II collagen induced immune balance of main subtype of helper T cells in mesenteric lymph node lymphocytes in rats with collagen-induced arthritis

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Abstract

Objective

To investigate the effect of the oral administration of chicken type II collagen (CCII) on T cells from mesenteric lymph node (MLN) lymphocytes in rats with collagen-induced arthritis (CIA).

Methods

CIA was induced in male Sprague-Dawley rats immunized with CCII in Freund’s complete adjuvant. CCII (10, 20, and 40 μg kg−1 day−1, i.g. × 7 days) was administered orally to rats from day 14 to 21 after immunization. Arthritis was evaluated by hind paw swelling and polyarthritis index, and MLNs and synovium were harvested for histological examination. Activity of interleukin-2 (IL-2) in MLN lymphocyte supernatant was measured by ConA-induced splenocyte proliferation in C57BL/6J mice, and IL-4, IL-17, and transforming growth factor beta (TGF-β) levels in MLN lymphocytes were measured by enzyme-linked immunosorbent assay (ELISA). The proportion of CD4+CD25+ Treg cells and Th17 cells was determined by double-color labeling for flow cytometry analysis.

Results

The administration of CCII (10, 20, 40 μg/kg, i.g. × 7 days) suppressed secondary inflammatory reactions and histological changes in CIA model. The activity of IL-2 and IL-17 produced by MLN lymphocytes from CIA rats was significantly inhibited by the administration of CCII (10, 20, and 40 μg kg−1 day−1). The levels of IL-4 and TGF-β were increased in CCII (10, 20, and 40 μg kg−1 day−1) groups. The flow cytometry analysis showed that CCII (10, 20, and 40 μg kg−1 day−1) significantly increased the proportion of Treg and decreased the proportion of Th17.

Conclusion

These results indicate that oral administration of CCII had therapeutic effects on CIA rats, which was related to decreased production of pro-inflammatory mediators (IL-2, IL-17) and increased production of anti-inflammatory mediators (IL-4, TGF-β). This suggests that CCII plays an important role in regulating the immune balance of Th1/Th2 and Th17/Treg in rats with CIA.

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References

  1. Steinman L. A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage. Nat Med. 2007;13:139–45.

    Article  PubMed  CAS  Google Scholar 

  2. McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007;7:429–42.

    Article  PubMed  CAS  Google Scholar 

  3. Falgarone G, Duclos M, Boissier MC. TNF-α antagonists in rheumatoid arthritis patients seen in everyday practice. Joint Bone Spine. 2007;74:523–6.

    Article  PubMed  CAS  Google Scholar 

  4. Shahabi S, Hassan ZM, Jazani NH, Ebtekar M. Sympathetic nervous system plays an important role in the relationship between immune mediated diseases. Med Hypotheses. 2006;67:900–3.

    Article  PubMed  CAS  Google Scholar 

  5. Fishman-Lobell J, Freidman A, Weiner HL. Different kinetic patterns of cytokine gene expression in vivo in orally tolerant mice. Eur J Immunol. 1994;24:2720–4.

    Article  PubMed  CAS  Google Scholar 

  6. Tsuji NM, Mizumachi K, Kurisaki J. Interleukin-10 secreting Peyer’s patch cells are responsible for active suppression in low-dose oral tolerance. Immunology. 2001;103:458–64.

    Article  PubMed  CAS  Google Scholar 

  7. Weiner HL. Oral tolerance: immune mechanisms and treatment of autoimmune diseases. Immunol Today. 1997;18:335–43.

    Article  PubMed  CAS  Google Scholar 

  8. Yao ZQ, Li R, Li ZG. A triple altered collagen II peptide with consecutive substitutions of TCR contacting residues inhibits collagen-induced arthritis. Ann Rheum Dis. 2007;66:423–4.

    Article  PubMed  CAS  Google Scholar 

  9. Myers LK, Sakurai Y, Rosloniec EF, Stuart JM, Kang AH. An analog peptide that suppresses collagen-induced arthritis. Am J Med Sci. 2004;327:212–6.

    Article  PubMed  Google Scholar 

  10. Sakurai Y, Brand DD, Tang B, Rosloniec EF, Stuart JM, Kang AH, et al. Analog peptides of type II collagen can suppress arthritis in HLA-DR4 (DRB1*0401) transgenic mice. Arthritis Res Ther. 2006;8:R150.

    Article  PubMed  CAS  Google Scholar 

  11. Wu H, Wei W, Song LH, Zhang LL, Chen Y, Hu XY. Paeoniflorin induced immune tolerance of mesenteric lymph node lymphocytes via enhancing beta 2-adrenergic receptor desensitization in rats with adjuvant arthritis. Int Immunopharmacol. 2007;7:662–73.

    Article  PubMed  CAS  Google Scholar 

  12. Zheng YQ, Wei W, Shen YX, Dai M, Liu LH. Oral and nasal administration of chicken type II collagen suppresses adjuvant arthritis in rats with intestinal lesions induced by meloxicam. World J Gastroenterol. 2004;10:3165–70.

    PubMed  CAS  Google Scholar 

  13. Mizrahi M, Ilan Y. The gut mucosa as a site for induction of regulatory T-cells. Curr Pharm Des. 2009;15:1191–202.

    Article  PubMed  CAS  Google Scholar 

  14. Thompson HS, Staines NA. Gastric administration of type II collagen delays the onset and severity of collagen-induced arthritis in rats. Clin Exp Immunol. 1986;64:581–6.

    PubMed  CAS  Google Scholar 

  15. Nagler-Anderson C, Bober LA, Robinson ME, Siskind GW, Thorbecke GJ. Suppression of type II collagen-induced arthritis by intragastric administration of soluble type II collagen. Proc Natl Acad Sci USA. 1986;83:7443–6.

    Article  PubMed  CAS  Google Scholar 

  16. Garcia G, Komagata Y, Slavin AJ, Maron R, Weiner HL. Suppression of collagen-induced arthritis by oral or nasal administration of type II collagen. J Autoimmun. 1999;13:315–24.

    Article  PubMed  CAS  Google Scholar 

  17. Zhang ZY, Lee CS, Lider O, Weiner HL. Suppression of adjuvant arthritis in Lewis rats by oral administration of type II collagen. J Immunol. 1990;145:2489–93.

    PubMed  CAS  Google Scholar 

  18. Yoshino S, Quattrocchi E, Weiner HL. Suppression of antigen-induced arthritis in Lewis rats by oral administration of type II collagen. Arthritis Rheum. 1995;38:1092–6.

    Article  PubMed  CAS  Google Scholar 

  19. Thompson SJ, Thompson HS, Harper N, Day MJ, Coad AJ, Elson CJ, et al. Prevention of pristane-induced arthritis by the oral administration of type II collagen. Immunology. 1993;79:152–7.

    PubMed  CAS  Google Scholar 

  20. Min SY, Hwang SY, Park KS, Lee JS, Lee KE, Kim KW, et al. Induction of IL-10-producing CD4+CD25+ T cells in animal model of collagen-induced arthritis by oral administration of type II collagen. Arthritis Res Ther. 2004;6:213–20.

    Article  CAS  Google Scholar 

  21. Ding CH, Li Q, Xiong ZY, Zhou AW, Jones G, Xu SY. Oral administration of type II collagen suppresses pro-inflammatory mediator production by synoviocytes in rats with adjuvant arthritis. Clin Exp Immunol. 2003;132:416–23.

    Article  PubMed  CAS  Google Scholar 

  22. Zhang LL, Wei W, Xiao F, Xu JH, Bao CD, Ni LQ, et al. A randomized, double-blind, multi-center, controlled clinical trial of chicken type II collagen in rheumatoid arthritis. Arthritis Rheum. 2008;59:905–10.

    Article  PubMed  CAS  Google Scholar 

  23. Feldmann M, Brennan FM, Maini RN. Rheumatoid arthritis. Cell. 1996;85:307–10.

    Article  PubMed  CAS  Google Scholar 

  24. Boissier MC, Assier E, Falgarone G, Bessis N. Shifting the imbalance from Th1/Th2 to Th17/Treg: the changing rheumatoid arthritis paradigm. Joint Bone Spine. 2008;75:373–5.

    Article  PubMed  CAS  Google Scholar 

  25. Wilson NJ, Boniface K, Chan JR, McKenzie BS, Blumenschein WM, Mattson JD, et al. Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol. 2007;8:950–7.

    Article  PubMed  CAS  Google Scholar 

  26. Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A, Sallusto F. Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol. 2007;8:942–9.

    Article  PubMed  CAS  Google Scholar 

  27. Chabaud M, Durand JM, Buchs N, Fossiez F, Page G, Frappart L, et al. Human interleukin-17: a T cell-derived proinflammatory cytokine produced by the rheumatoid synovium. Arthritis Rheum. 1999;42:963–70.

    Article  PubMed  CAS  Google Scholar 

  28. Miossec P. Interleukin-17 in rheumatoid arthritis: if T cells were to contribute to inflammation and destruction through synergy. Arthritis Rheum. 2003;48:594–601.

    Article  PubMed  CAS  Google Scholar 

  29. Evans HG, Suddason T, Jackson I, Taams LS, Lord GM. Optimal induction of T helper 17 cells in humans requires T cell receptor ligation in the context of Toll-like receptor-activated monocytes. Proc Natl Acad Sci USA. 2007;104:17034–9.

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank Dr. Qing Li and Dr. WenDi Zhao for technical assistance and Dr. GuoDong Shen for manipulation. This work was supported by the National Natural Science Foundation of China (no. 30572356, no. 30973543), by the Natural Science Foundation of the Education Department of Anhui Province (no. KJ2008B295), by the Scientific Research Foundation of Anhui Medical University (no. 2008kj13), and by the scientific research funds of Dr. Zhang LingLing (XJ200808).

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Correspondence to Wei Wei.

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Responsible Editor: J. Di Battista.

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Tong, T., Zhao, W., Wu, YQ. et al. Chicken type II collagen induced immune balance of main subtype of helper T cells in mesenteric lymph node lymphocytes in rats with collagen-induced arthritis. Inflamm. Res. 59, 369–377 (2010). https://doi.org/10.1007/s00011-009-0109-4

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  • DOI: https://doi.org/10.1007/s00011-009-0109-4

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