title: 1,25(OH)2D3 prolongs islet graft survival by inflammatory inhibition.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Z-Z
authors.initials: ZZ
authors.lastname: Jiao
authors.affiliation: 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.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: 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.
authors.forename: P
authors.initials: P
authors.lastname: Fan
authors.affiliation: Department of Hepatobiliary, the First Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an City, Shannxi Province, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: W-J
authors.initials: WJ
authors.lastname: Xue
authors.affiliation: 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.
authors.forename: X-M
authors.initials: XM
authors.lastname: Ding
authors.affiliation: 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.
authors.forename: X-H
authors.initials: XH
authors.lastname: Tian
authors.affiliation: 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.
authors.forename: X-S
authors.initials: XS
authors.lastname: Feng
authors.affiliation: 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.
authors.forename: J
authors.initials: J
authors.lastname: Zheng
authors.affiliation: 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.
authors.forename: P-X
authors.initials: PX
authors.lastname: Tian
authors.affiliation: 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.
authors.forename: C-G
authors.initials: CG
authors.lastname: Ding
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: X-H
authors.initials: XH
authors.lastname: Fan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002117:Calcitriol / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006085:Graft Survival / Q000187:drug effects*; D007249:Inflammation / Q000517:prevention & control*; D016381:Islets of Langerhans Transplantation; D008264:Macrophages / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002117:Calcitriol