Z-Z Jiao1, Y Li2, P Fan3, J Guo4, W-J Xue1, X-M Ding1, X-H Tian1, X-S Feng1, J Zheng1, P-X Tian1, C-G Ding1, X-H Fan5. 1. Department of Renal Transplantation, Hospital of Nephrology, the First Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an City, Shannxi Province, People's Republic of China. 2. Department of Renal Transplantation, Hospital of Nephrology, the First Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an City, Shannxi Province, People's Republic of China. Electronic address: jullian80915@126.com. 3. Department of Rheumatism and Immunology, the First Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an City, Shannxi Province, People's Republic of China. 4. Department of Hepatobiliary, the First Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an City, Shannxi Province, People's Republic of China. 5. Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
Abstract
OBJECTIVE: This study aimed to determine the protective effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) against islet graft loss. METHODS: Proliferation of tumor necrosis factor (TNF)-α-induced macrophages was determined in vitro after treatment with different concentrations of 1,25-(OH)2D3. Intraportal islet transplantation (IPIT) was performed with islets harvested from the Sprague-Dawley rats and transplanted to the diabetic rats. The transplanted rats were assigned to receive 1,25-(OH)2D3 or propylene glycol (control). Islet graft survival; inflammatory cytokine (TNF-α and interleukin [IL]-1); numbers and percentages of macrophages, CD4(+), and CD8(+) T cells in bloods; and expression of nuclear factor (NF)-κB and TNF-α were analyzed. Hematoxylin and eosin staining was performed. RESULTS: We found 100 mg/mL 1,25-(OH)2D3 per day to have the strongest inhibitory effect on macrophages. Survival time of islet grafts significantly increased in the rats receiving 1,25-(OH)2D3. There were fewer infiltrated inflammatory cells in both islet graft and adjacent tissue in the drug-treated rats with lower serum IL-1 and TNF-α. Furthermore, percentage of macrophages and expression of p-NF-κB p65 and TNF-α in graft sites were significantly lower in the treated rats. CONCLUSION: Our results demonstrated that 1,25(OH)2D3 prolongs islet graft survival by decreasing nonspecific inflammation in syngeneic IPIT through inhibiting TNF-α/NF-κB pathway and macrophage infiltration.
OBJECTIVE: This study aimed to determine the protective effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) against islet graft loss. METHODS: Proliferation of tumor necrosis factor (TNF)-α-induced macrophages was determined in vitro after treatment with different concentrations of 1,25-(OH)2D3. Intraportal islet transplantation (IPIT) was performed with islets harvested from the Sprague-Dawley rats and transplanted to the diabeticrats. The transplanted rats were assigned to receive 1,25-(OH)2D3 or propylene glycol (control). Islet graft survival; inflammatory cytokine (TNF-α and interleukin [IL]-1); numbers and percentages of macrophages, CD4(+), and CD8(+) T cells in bloods; and expression of nuclear factor (NF)-κB and TNF-α were analyzed. Hematoxylin and eosin staining was performed. RESULTS: We found 100 mg/mL 1,25-(OH)2D3 per day to have the strongest inhibitory effect on macrophages. Survival time of islet grafts significantly increased in the rats receiving 1,25-(OH)2D3. There were fewer infiltrated inflammatory cells in both islet graft and adjacent tissue in the drug-treated rats with lower serum IL-1 and TNF-α. Furthermore, percentage of macrophages and expression of p-NF-κB p65 and TNF-α in graft sites were significantly lower in the treated rats. CONCLUSION: Our results demonstrated that 1,25(OH)2D3 prolongs islet graft survival by decreasing nonspecific inflammation in syngeneic IPIT through inhibiting TNF-α/NF-κB pathway and macrophage infiltration.