title: Hemo oxygenase-1 induction in vitro and in vivo can yield pancreas islet xenograft survival and improve islet function.
abstract: BACKGROUND
  The induced expression of heme oxygenase-1 (HO-1) in donor islets improves allograft survival. Cobalt protoporphyrin (CoPP) could significantly enhance the expression of HO-1 mRNA and protein in rat islet safely. Our work was to study how to protect pancreatic islet xenograft by CoPP-induction.
  
  
  METHODS
  Islet xenografts treated with CoPP-induction and CoPP + Zinc protoporphyrin (ZnPP) in vitro and in vivo were randomly transplanted into murine subrenal capsule; then the graft survival time was compared by blood glucose level and pathological examination and meanwhile the interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin 10 (IL-10) and IL-1β level in serum and their mRNA and HO-1 mRNA and protein expression were examined.
  
  
  RESULTS
  Islets with CoPP-induction under low- and high-glucose stimulation exhibited much higher insulin secretion compared with other three groups. CoPP-induction could increase higher expression of HO-1 (mRNA: 3.33- and 76.09-fold in vitro and in vivo; protein: 2.85- and 58.72-fold). The normoglycemia time in induction groups ((14.63 ± 1.19) and (16.88 ± 1.64) days) was significantly longer. The pathological examination showed less lymphocyte infiltration in induction groups. The IL-10 level and its mRNA in induction groups were significantly higher.
  
  
  CONCLUSIONS
  The HO-1 induced by CoPP would significantly improve function, prolong normoglycemia time and reduce lymphocyte infiltration. Meanwhile CoPP-induction in vivo had more beneficial effects than in vitro. Its mechanism could be related to immune-modulation of IL-10.
authors.affiliation: Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Chang
authors.initials: C
authors.lastname: Su
authors.forename: Zheng-Yun
authors.initials: ZY
authors.lastname: Zhang
authors.forename: Ming-Jun
authors.initials: MJ
authors.lastname: Zhang
authors.forename: Wei-Qiong
authors.initials: WQ
authors.lastname: Gu
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Li
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Li
authors.forename: Guang-Wen
authors.initials: GW
authors.lastname: Zhou
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006085:Graft Survival; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D016753:Interleukin-10 / Q000097:blood; D007515:Islets of Langerhans / Q000201:enzymology / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous
chemical_list: D016753:Interleukin-10; D051547:Heme Oxygenase-1