title: Blockade of the nuclear factor kappa B pathway prolonged islet allograft survival.
abstract: Nuclear factor kappa B (NF-κB) pathway is known for its important role in the upregulation of various inflammatory mediators and its "switch regulator" functionality for transcription factor gene networks which control cytokine-induced β-cell dysfunction and death. In this study, the islets were divided into the control group, Ad-green fluorescent protein, and the adenovirus transfected with inhibitor kappa B group. The proliferation index of peripheral blood mononuclear cells and the islets apoptosis index were examined after mixed lymphocyte-islet reaction with inverted fluorescence microscopy. Moreover, mRNA expression of inflammatory cytokines was measured by reverse transcription polymerase chain reaction. The islet graft survival time in diabetic rats, insulin in grafts, and cytokine concentrations in the supernatant were determined by immunohistochemistry and enzyme-linked immunosorbent assay. We found that blocking of NF-κB activation in β-cells significantly downregulated inflammatory chemokine production by islets cells in vitro and in vivo, inhibited T-cell recruitment into the pancreatic islets, inhibited β-cell dysfunction, and effectively prolonged the survival time of islet grafts. The results presented in this work highlight a novel mechanism of blocking NF-κB activation in β-cells for the treatment of islet cell transplantation.
authors.affiliation: Department of Renal Transplant, Center of Nephropathy, the First Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an City, Shaanxi Province, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Ding
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.forename: Wujun
authors.initials: W
authors.lastname: Xue
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Tian
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Fengmei
authors.initials: F
authors.lastname: Jiao
authors.forename: Xinshun
authors.initials: X
authors.lastname: Feng
authors.forename: Jin
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000818:Animals; D002470:Cell Survival; D016207:Cytokines / Q000276:immunology; D003920:Diabetes Mellitus / Q000601:surgery*; D006085:Graft Survival; D018836:Inflammation Mediators / Q000276:immunology; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology* / Q000276:immunology; D016381:Islets of Langerhans Transplantation; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D007328:Insulin; D016328:NF-kappa B