system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Allografts, Animals, CD4-Positive T-Lymphocytes, Corneal Transplantation, Cyclosporine, Cytokines, Dexamethasone, Drug Therapy, Combination, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Graft Rejection, Graft Survival, Immunosuppressive Agents, Injections, Intraperitoneal, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, RNA, Messenger, Receptors, Lysosphingolipid, Sirolimus, T-Lymphocytes, Regulatory.
user
Does systemic application of sphingosine 1-phosphate receptor 1 immunomodulator inhibit corneal allograft rejection in mice? Context: This study aims to investigate the effects of systemic application of sphingosine 1-phosphate receptor 1(S1P1) on allogeneic corneal transplantation in mice. 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. 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.
assistant
S1P1 has significant effect in corneal allograft rejection inhibition. The combined treatment of S1P1 and rapamycin results in synergistic effect. Final Decision: yes