Open AccessKnockdown of Intraislet IKKβ by Spherical Nucleic Acid Conjugates Prevents Cytokine-Induced Injury and Enhances Graft Survival
Author(s) -
Jonathan S. Rink,
Kaylin M. McMahon,
Xiaomin Zhang,
Xiaojuan Chen,
Chad A. Mirkin,
C. Shad Thaxton,
Dixon B. Kaufman
Publication year - 2013
Publication title -
transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.45
H-Index - 204
eISSN - 1534-6080
pISSN - 0041-1337
DOI - 10.1097/tp.0b013e3182a4190e
Subject(s) - proinflammatory cytokine , islet , gene knockdown , transplantation , iκb kinase , cytokine , small interfering rna , biology , cancer research , nf κb , apoptosis , immunology , chemistry , microbiology and biotechnology , endocrinology , medicine , inflammation , cell culture , biochemistry , transfection , diabetes mellitus , genetics
The efficiency of islet graft survival after intraportal implantation is compromised by host innate immune responses and the production of proinflammatory cytokines that cause acute cellular injury. This reaction activates intraislet nuclear factor-κB (NF-κB), causing production of gene products that have detrimental effects on β-cell survival and function. We hypothesized that small interfering RNA targeting of IKKβ, a crucial kinase in the NF-κB activation pathway, in islets before transplantation would ameliorate the detrimental effects of cytokines and improve islet survival after transplantation.