Open Access

IL‑15 is decreased upon CsA and FK506 treatment of acute rejection following heart transplantation in mice

  • Authors:
    • Zhiyong Yu
    • Xiaoping Zhou
    • Songfeng Yu
    • Haiyang Xie
    • Shusen Zheng
  • View Affiliations

  • Published online on: October 20, 2014     https://doi.org/10.3892/mmr.2014.2703
  • Pages: 37-42
  • Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The aim of this study was to investigate the effect of cyclosporine A (CsA) and tacrolimus (FK506) on interleukin‑15 (IL‑15) production during acute rejection following heart transplantation in mice. Inbred male Balb/c (H‑2d) and C57BL/6 (H‑2b) mice were used to establish a heterotopic intra‑abdominal cardiac transplantation model. The mice were divided in four groups: syngeneic control, allogeneic acute rejection, allogeneic rejection treated with CsA, and allogeneic rejection treated with FK506. The expression of IL‑15, IL‑2, and tumor necrosis factor‑α (TNF‑α) was measured using reverse transcription‑polymerase chain reaction (RT‑PCR) and western blotting. A low level of IL‑15 was detected in transplanted hearts of the control group, with a significant increase observed in the allogeneic acute rejection group. Compared to the allogeneic acute rejection group, IL‑15 expression was significantly decreased in the CsA‑and FK506‑treated allogeneic rejection groups. The TNF‑α expression pattern was similar to that of IL‑15 in all groups. IL‑2 expression was increased in the allogeneic acute rejection group and was inhibited in mice treated with CsA and FK506. In conclusion, increased IL‑15 expression in rejected murine heart grafts may be reduced by CsA and FK506 in vivo.

References

1 

van Gelder T, Baan CC, Balk AH, et al: Blockade of the interleukin (IL)-2/IL-2 receptor pathway with a monoclonal anti-IL-2 receptor antibody (BT563) does not prevent the development of acute heart allograft rejection in humans. Transplantation. 65:405–410. 1998.PubMed/NCBI

2 

Li XC, Roy-Chaudhury P, Hancock WW, et al: IL-2 and IL-4 double knockout mice reject islet allografts: a role for novel T cell growth factors in allograft rejection. J Immunol. 161:890–896. 1998.PubMed/NCBI

3 

Steiger J, Nickerson PW, Steurer W, Moscovitch-Lopatin M and Strom TB: IL-2 knockout recipient mice reject islet cell allografts. J Immunol. 155:489–498. 1995.PubMed/NCBI

4 

Lewis EC, Weiler M, Tejman-Yarden N, et al: Involvement of graft-derived interleukin-15 in islet allograft rejection in mice. Cytokine. 34:106–113. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Zheng XX, Gao W, Donskoy E, et al: An antagonist mutant IL-15/Fc promotes transplant tolerance. Transplantation. 81:109–116. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Ikemizu S, Chirifu M and Davis SJ: IL-2 and IL-15 signaling complexes: different but the same. Nat Immunol. 13:1141–1142. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Ring AM, Lin JX, Feng D, et al: Mechanistic and structural insight into the functional dichotomy between IL-2 and IL-15. Nat Immunol. 13:1187–1195. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Waldmann TA: The IL-2/IL-15 receptor systems: targets for immunotherapy. J Clin Immunol. 22:51–56. 2002. View Article : Google Scholar : PubMed/NCBI

9 

Grabstein KH, Eisenman J, Shanebeck K, et al: Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor. Science. 264:965–968. 1994. View Article : Google Scholar : PubMed/NCBI

10 

Di Sabatino A, Calarota SA, Vidali F, MacDonald TT and Corazza GR: Role of IL-15 in immune-mediated and infectious diseases. Cytokine Growth Factor Rev. 22:19–33. 2011.PubMed/NCBI

11 

van Es T, van Puijvelde GH, Michon IN, et al: IL-15 aggravates atherosclerotic lesion development in LDL receptor deficient mice. Vaccine. 29:976–983. 2011.PubMed/NCBI

12 

d‘Ettorre G, Andreotti M, Ceccarelli G, et al: The role of IL-15 in challenging Acquired Immunodeficiency Syndrome. Cytokine. 57:54–60. 2012.PubMed/NCBI

13 

Croce M, Orengo AM, Azzarone B and Ferrini S: Immunotherapeutic applications of IL-15. Immunotherapy. 4:957–969. 2012. View Article : Google Scholar

14 

Roberti MP, Rocca YS, Amat M, et al: IL-2- or IL-15-activated NK cells enhance Cetuximab-mediated activity against triple-negative breast cancer in xenografts and in breast cancer patients. Breast Cancer Res Treat. 136:659–671. 2012. View Article : Google Scholar

15 

Steel JC, Waldmann TA and Morris JC: Interleukin-15 biology and its therapeutic implications in cancer. Trends Pharmacol Sci. 33:35–41. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Baan CC, van Riemsdijk-Overbeeke IC, Boelaars-van Haperen MJ, Ijzermans JM and Weimar W: Inhibition of the IL-15 pathway in anti-CD25 mAb treated renal allograft recipients. Transpl Immunol. 10:81–87. 2002. View Article : Google Scholar : PubMed/NCBI

17 

Smith XG, Bolton EM and Bradley JA: Targeting IL-15 as a therapeutic strategy in organ transplant rejection. Curr Opin Investig Drugs. 3:406–410. 2002.PubMed/NCBI

18 

Cho ML, Kim WU, Min SY, et al: Cyclosporine differentially regulates interleukin-10, interleukin-15, and tumor necrosis factor α production by rheumatoid synoviocytes. Arthritis Rheum. 46:42–51. 2002.PubMed/NCBI

19 

Lewis E, Weiler M, Chaimovitz C and Douvdevani A: Interleukin-15 is the main mediator of lymphocyte proliferation in cultures mixed with human kidney tubular epithelial cells. Transplantation. 72:886–890. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Stoeck M, Schäfer M, Hofmann HP and Gekeler V: Dexamethasone and cyclosporin A do not inhibit interleukin-15 expression in the human lung carcinoma cell line A549. Eur Cytokine Netw. 11:414–419. 2000.PubMed/NCBI

21 

Ono K and Lindsey ES: Improved technique of heart transplantation in rats. J Thorac Cardiovasc Surg. 57:225–229. 1969.PubMed/NCBI

22 

Giri JG, Ahdieh M, Eisenman J, et al: Utilization of the beta and gamma chains of the IL-2 receptor by the novel cytokine IL-15. EMBO J. 13:2822–2830. 1994.PubMed/NCBI

23 

Hubscher SG: Histological findings in liver allograft rejection - new insights into the pathogenesis of hepatocellular damage in liver allografts. Histopathology. 18:377–383. 1991. View Article : Google Scholar : PubMed/NCBI

24 

McCaughan GW, Davies JS, Waugh JA, et al: A quantitative analysis of T lymphocyte populations in human liver allografts undergoing rejection: the use of monoclonal antibodies and double immunolabeling. Hepatology. 12:1305–1313. 1990. View Article : Google Scholar

25 

Wiederrecht G, Lam E, Hung S, Martin M and Sigal N: The mechanism of action of FK-506 and cyclosporin A. Ann NY Acad Sci. 696:9–19. 1993. View Article : Google Scholar : PubMed/NCBI

26 

Yamamoto S and Kato R: Hair growth-stimulating effects of cyclosporin A and FK506, potent immunosuppressants. J Dermatol Sci. (Suppl): S47–S54. 1994. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

January 2015
Volume 11 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Yu, Z., Zhou, X., Yu, S., Xie, H., & Zheng, S. (2015). IL‑15 is decreased upon CsA and FK506 treatment of acute rejection following heart transplantation in mice. Molecular Medicine Reports, 11, 37-42. https://doi.org/10.3892/mmr.2014.2703
MLA
Yu, Z., Zhou, X., Yu, S., Xie, H., Zheng, S."IL‑15 is decreased upon CsA and FK506 treatment of acute rejection following heart transplantation in mice". Molecular Medicine Reports 11.1 (2015): 37-42.
Chicago
Yu, Z., Zhou, X., Yu, S., Xie, H., Zheng, S."IL‑15 is decreased upon CsA and FK506 treatment of acute rejection following heart transplantation in mice". Molecular Medicine Reports 11, no. 1 (2015): 37-42. https://doi.org/10.3892/mmr.2014.2703