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Blockade of the Nuclear Factor Kappa B Pathway Prolonged Islet Allograft Survival
Author(s) -
Ding Xiaoming,
Wang Xiaohong,
Xue Wujun,
Tian Xiaohui,
Li Yang,
Jiao Fengmei,
Feng Xinshun,
Zheng Jin
Publication year - 2012
Publication title -
artificial organs
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.684
H-Index - 76
eISSN - 1525-1594
pISSN - 0160-564X
DOI - 10.1111/j.1525-1594.2011.01395.x
Subject(s) - islet , downregulation and upregulation , transplantation , apoptosis , cytokine , nfkb1 , peripheral blood mononuclear cell , biology , transcription factor , chemistry , microbiology and biotechnology , cancer research , endocrinology , medicine , immunology , in vitro , insulin , biochemistry , gene
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.