Effects of transforming growth factor-beta1 on tumor necrosis factor-alpha expression of corneal allografts during acute immunological rejection in rats

doi:10.3969/j.issn.2095-4344.2015.05.021

Abstract

Abstract:

BACKGROUND: Allogeneic penetrating keratoplasty is the most effective method for treating corneal blindness. However, the incidence of rejections is high after keratoplasty, so it is urgent to develop an immunosuppressive drug with high efficacy and low toxicity.
OBJECTIVE: To establish allogeneic penetrating keratoplasty models and monitor the expression of tumor necrosis factor-α in blank control group and after transforming growth factor-β1 eyedrop during acute rejection period of corneal grafts.
METHODS: Allogeneic penetrating keratoplasty models were established and were randomly divided into blank control group, ciclosporin A group (1% ciclosporin A), and transforming growth factor-β1 group (1 μg/ml transforming growth factor-β1 eyedrop). The medications from each group commenced at 1 day after surgery, one eyedrop once, three eyedrops per day. All the operated eyes were given 0.3% ofloxacin ophthalmic solutions and 0.5% tropicaide ophthalmic solution, three times per day, for 12 days. The corneal grafts were harvested for hematoxylin-eosin staining and immunihistochemical staining (SABC method), to detect tumor necrosis factor-α expression in corneal grafts.
RESULTS AND CONCLUSION: Hematoxylin-eosin staining showed that, corneal grafts were significantly thickened, a large number of histoleucocytes and lymphocytes infiltrated in the blank control group; corneal grafts showed normal thickness and no inflammatory cells infiltrated in the transforming growth factor-β1 group. Immunohistochemical staining showed that, there were less cells positive for tumor necrosis factor-α in the transforming growth factor-β1 group compared with the blank control group (P < 0.05). Transforming growth factor-β1 eyedrops can reduce the expression of tumor necrosis factor-α in the corneal grafts during acute rejection period, and reduce the inflammatory cells infiltration in the corneal grafts, which is probably the mechanism of transforming growth factor-β1 to prevent and treat corneal allograft rejection.

中国组织工程研究杂志出版内容重点：肾移植；肝移植；移植；心脏移植；组织移植；皮肤移植；皮瓣移植；血管移植；器官移植；组织工程

全文链接：

Key words: Corneal Transplantation, Graft Rejection, Transforming Growth Factor beta1, Tumor Necrosis Factor-alpha

CLC Number:

R318

Wang Heng, Lu Xiao-he, Zuo Wei. Effects of transforming growth factor-beta1 on tumor necrosis factor-alpha expression of corneal allografts during acute immunological rejection in rats[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(5): 778-782.

Figures/Tables 3

References

[1] Vail A , Gore SM, Bradley BA, et al. Conclusions of the corneal transplant follow up study. Br J Ophthalmol.1997;81: 631-636.
[2] Eurich D,Neumann UP,Boas-Knoop S,et al.Transforming growth factor-β1-gene polymorphism in the development of kidney diseaseafter liver transplantation.Transplantation. 2012;93(5 ):555-560.
[3] Tanabe T,Kanoh S,Moskowitz WB,et al.Cardiac asthma: transforming growth factor-β from the failing heart leads to squamous metaplasia in human airway cells and in the murine lung.Chest.2012;142(5):1274-1283.
[4] de Menezes Neves PD, Machado JR, dos Reis MA, et al. Distinct expression of interleukin 17,tumor necrosis factor α,transforming growth factor β,and forkhead box P3 in acute rejection after kidneytransplantation. Ann Diagn Pathol.2013; 17(1):75-79．
[5] Huss DJ,Winger RC,Peng H,et al.TGF-beta enhances effector Th1 cell activation but promotes self-regulation via IL-10.Immunol.2010;184(10):5628-5636.
[6] Hu B,He Y,Wu Y,et al.Activated allogeneic NK cells as suppressorsof alloreactive responses. Biol Blood Marrow Transplant.2010;16(6) :772-781．
[7] Han KL,Thomas SV,Koontz SM,et al.Adenosine A-A receptoragonist-mediated increase in donor-derived regulatory T cells suppressesdevelopment of graft-versus- host disease.J Immunol.2013;190(1):458-468．
[8] Wu LM,Zhou L,Xu J, et al.Lack of association between genetic polymorphisms in cytokine genes and tumor recurrence in patients with hepatocellular carcinoma undergoing transplantation.Hepatobiliary Pancreat Dis Int. 2013;12(1):54-59．
[9] Le Texier L,Thebault P,Carvalho-Gaspar M, et al. Immunoregulatory function of IL-27 and TGF-β1 in cardiac allograft transplantation.Transplantation.2012;94(3):226-233.
[10] Williams KA,Coster DJ.Penetrating corneal transplantation in the inbred rat:a new model.Invest Ophthalmol Vis Sci. 1985; 26(1):23-30.
[11] Torres PF, De Vos AF, Van der Gaag R, et al. CytokinemRNA expression during experimental corneal allograft rejection. J Exp Eye Res 2006;63:453-461.
[12] Sano Y, Osawa H, Sotozono C, et al. Cytokine expression during orthotopic corneal allograft rejection in mice.Invest Ophthalmol Vis Sci 2008; 39:1953-1957.
[13] Zhu S, Dekaris I, Duncker G, et al. Early expression of proinflammato rycytokines interleukin and tumor necrosis factor alpha after corneal transplantation. J Interferon Cytokine Res. 2009;19(6):661-669.
[14] 张新华,钟翠平,周播江,等.转化生长因子β1基因修饰树突状细胞延长移植心脏存活时间的研究[J].现代免疫学,2004, 24(6): 464-469
[15] DePaz HA, Oluwole OO, Adeyeri AO, et al. Immature rat myeloid dendritic cells generated in low-dose granulocyte macrophage-colony stimulating factor prolong donor specific rat cardiac allograft survival. Transplantation. 2003; 75(4): 521-552.
[16] 闫峰,蔡莉,惠延年,等.TGFβ2-DC对小鼠同种异体角膜移植排斥反应的抑制作用[J].国际眼科杂志, 2007,7(2):346-349.