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

Abstract

. 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.

mTORC1 regulates apoptosis and cell proliferation in pterygium via targeting autophagy and FGFR3

“…In skin cancer, unbalanced mTOR signalling leads to UV-induced hyperproliferation and malignant transformation, thus indicating that mTOR may be involved in pterygium pathology 6 . Other studies have found that rapamycin inhibits corneal neovascularisation 7 , transplant rejection 8 and the epithelial-to-mesenchymal transition (EMT) of the lens epithelium 9 . Moreover, rapamycin has also been reported to promote the apoptosis of human lens epithelial cells (LECs) and to inhibit the proliferation of rabbit LECs 10 – 12 .…”

mTOR Inhibition Mitigates Molecular and Biochemical Alterations of Vigabatrin-Induced Visual Field Toxicity in Mice

“…Along these lines, ocular administration of rapamycin has improved the engraftment of corneal allografts. 30,31 Rapalog administration directly to the eye (either intravitreally or subretinally, the latter requiring specialized equipment) could be advantageous in bypassing the potential for systemic toxicity associated with rapalogs. Pharmaceuticals that eliminate the retinal toxicity of VGB would provide a major advance in epilepsy treatment, and our studies suggest that mTOR inhibitors should receive further preclinical attention as a therapeutic modality to potentially mitigate VGB-induced visual field pathology.…”

Rapeseed Oil and Ginseng Saponins Work Synergistically To Enhance Th1 and Th2 Immune Responses Induced by the Foot-and-Mouth Disease Vaccine

“…Serum gamma interferon (IFN-␥) levels were determined using an ELISA kit (MultiSciences Biotech Co., Ltd., Hangzhou, China) (17), and serum interleukin 5 (IL-5) levels were measured using an ELISA kit (eBioscience Inc., San Diego, CA, USA). Serum cytokine levels were evaluated by interpolation of cytokine standard curves.…”