Effects of different dose of FTY720 on lymphocyte cell cycle arrest in cardiac transplantation model of rats

Li, Qingyuan; Li, Feng

doi:10.3109/08923971003674433

Cited by 7 publications

(8 citation statements)

References 26 publications

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“…Previous studies also showed that FTY720 has positive efficacy on SCI in animal models after systemic administration. However, the side effects of FTY720 are dose-dependent [32,33]. The total dosage that we used (0.5 mg) is far less than that of the previous studies adopted (daily oral dosage of 1e3 mg/kg utilized for SCI at least 4 weeks).…”

Section: Discussionmentioning

confidence: 93%

Local delivery of FTY720 in PCL membrane improves SCI functional recovery by reducing reactive astrogliosis

Wang

Lü

et al. 2015

Biomaterials

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Section: Discussionmentioning

confidence: 93%

Local delivery of FTY720 in PCL membrane improves SCI functional recovery by reducing reactive astrogliosis

Wang

Lü

et al. 2015

Biomaterials

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“…However, FTY720, not a specific S1P1 agonist, exists the side effects. In this study, we showed that the selected S1P1 agonist can prolong the corneal graft survival as long as the reported FTY720, which is a non-selected S1P agonist and exist the side effects [25]. In 2011, Robert Wills and his colleagues found a S1P1 selective agonist, and made a series of comparisons with the FTY720.…”

Section: Discussionmentioning

confidence: 67%

Prolonging Survival of Corneal Transplantation by Selective Sphingosine-1-Phosphate Receptor 1 Agonist

et al. 2014

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Corneal transplantation is the most used therapy for eye disorders. Although the cornea is somewhat an immune privileged organ, immune rejection is still the major problem that reduces the success rate. Therefore, effective chemical drugs that regulate immunoreactions are needed to improve the outcome of corneal transplantations. Here, a sphingosine-1-phosphate receptor 1 (S1P1) selective agonist was systematically evaluated in mouse allogeneic corneal transplantation and compared with the commonly used immunosuppressive agents. Compared with CsA and the non-selective sphingosine 1-phosphate (S1P) receptor agonist FTY720, the S1P1 selective agonist can prolong the survival corneal transplantation for more than 30 days with a low immune response. More importantly, the optimal dose of the S1P1 selective agonist was much less than non-selective S1P receptor agonist FTY720, which would reduce the dose-dependent toxicity in drug application. Then we analyzed the mechanisms of the selected S1P1 selective agonist on the immunosuppression. The results shown that the S1P1 selective agonist could regulate the distribution of the immune cells with less CD4+ T cells and enhanced Treg cells in the allograft, moreover the expression of anti-inflammatory cytokines TGF-β1 and IL-10 unregulated which can reduce the immunoreactions. These findings suggest that S1P1 selective agonist may be a more appropriate immunosuppressive compound to effectively prolong mouse allogeneic corneal grafts survival.

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“…2007). As a new immunosuppressant, systemic treatment with FTY720 can prolong corneal graft survival, but with possible side‐effects (Li & Li 2010).…”

Section: Discussionmentioning

confidence: 99%

Systemic application of sphingosine 1‐phosphate receptor 1 immunomodulator inhibits corneal allograft rejection in mice

Zhu

Liu

et al. 2013

Acta Ophthalmologica

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. Purpose: This study aims to investigate the effects of systemic application of sphingosine 1‐phosphate receptor 1(S1P1) on allogeneic corneal transplantation in mice. Methods: A total of 112 BALB/c mice received corneal grafts from C57BL/6 donors. Recipients were randomly divided into seven groups and treated with intraperitoneal injections of S1P1 (5 mg/kg/days), cyclosporine A (5 mg/kg/days), dexamethasone (1 mg/kg/days) and rapamycin (2 mg/kg/days). S1P1was combined with rapamycin or cyclosporine A, and saline served as negative control. Serum levels of IL‐2, IL‐10, TGF‐β1 and IFN‐γ were measured by Elisa. The numbers of CD4+ T and regulatory (Treg) cell phenotype were measured by flow cytometry. Cytokine mRNA expression was analysed by real‐time quantitative PCR. CD4+ T cells and cytokines were histologically identified by immunofluorescence staining. Results: Corneal graft survival was prolonged by intraperitoneal injections in S1P1 alone (mean survival time MST, 35.3 ± 5.6 days), S1P1 combined with rapamycin (MST, 38.7 ± 6.5 days) or S1P1 and cyclosporine A (MST, 32.7 ± 4.8 days) compared with the controls (MST, 14.6 ± 0.2 days; n = 5, p < 0.01). S1P1 alone increased CD4+ T (p < 0.01) and Treg cells (p < 0.01; n = 5) in the cervical and mesenteric lymph nodes compared with the controls and S1P1 + rapamycin (p < 0.05; n = 5). TGF‐β1 and IL‐10 mRNA transcriptions in corneal grafts following S1P1+ rapamycin increased (both p < 0.01; n = 3), and TGF‐β1 and IL‐10 in the serum level following S1P1 alone increased (both p < 0.01; n = 3). These results paralleled the findings obtained from immunofluorescence. Conclusion: S1P1 has significant effect in corneal allograft rejection inhibition. The combined treatment of S1P1 and rapamycin results in synergistic effect.

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Effects of different dose of FTY720 on lymphocyte cell cycle arrest in cardiac transplantation model of rats

Abstract: FTY720 is an effective immunosuppressant and immunosuppressive effect of FTY720 show a tendency of time and dose dependent. Effect of cell cycle arrest of FTY720 is related to dose of this new immunosuppressant.

Cited by 7 publications

References 26 publications

Local delivery of FTY720 in PCL membrane improves SCI functional recovery by reducing reactive astrogliosis

Local delivery of FTY720 in PCL membrane improves SCI functional recovery by reducing reactive astrogliosis

Prolonging Survival of Corneal Transplantation by Selective Sphingosine-1-Phosphate Receptor 1 Agonist

Systemic application of sphingosine 1‐phosphate receptor 1 immunomodulator inhibits corneal allograft rejection in mice

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