TY - JOUR
T1 - Gene Expression Profiling of Human Pancreatic Islets Undergoing a Simulated Process of Instant Blood-Mediated Inflammatory Reaction
AU - Jackson, A.
AU - McWilliams, C.
AU - Kaizer, E.
AU - Chaussabel, D.
AU - Glaser, C.
AU - Noguchi, H.
AU - Matsumoto, S.
AU - Levy, M. F.
AU - Naziruddin, B.
PY - 2008/3
Y1 - 2008/3
N2 - Objective: Islet cell transplantation, as a treatment for type 1 diabetes mellitus, has historically required islet infusions from more than one donor organ to achieve insulin independence. Significant islet mass may be destroyed upon infusion due to a yet undefined process known as instant blood-mediated inflammatory reaction (IBMIR). Our objective was to identify gene expression changes in islets undergoing a simulated process of IBMIR. Materials and Methods: Human pancreatic islets were isolated from 2 cadaveric donors and divided into 3 groups each for a total of 18 samples. Group one (n = 3) was treated with autologous sera, group two (n = 3) with allogeneic sera, and group three (n = 3) with type 1 diabetic sera (T1DM). Each group was treated for 3 hours at 37°C. Islets were washed, lysed using TRI reagent, and mRNA was isolated using the Total Prep mRNA isolation kit. Isolated cRNA was used for microarray analysis using Illumina Gene Chips Hu6_v2. GeneSpring GX software was used for statistical analysis. Results were significant at P < .05. Results: One-way ANOVA statistical analysis of the microarray data revealed that interleukin-11 (IL-11), interleukin-12A (IL-12A), and Ras related associated with diabetes (RRAD) were overexpressed in islets exposed to diabetic sera when normalized to autologous control (P < .01). Under the same conditions, islet cells exposed to T1DM serum had down-regulation of IL-1 receptor antagonist (IL-1RN). Conclusion: These findings suggested that T1DM serum elicited an adaptive and innate immune response to the transplanted islet mass making them more susceptible to cytokine-mediated destruction.
AB - Objective: Islet cell transplantation, as a treatment for type 1 diabetes mellitus, has historically required islet infusions from more than one donor organ to achieve insulin independence. Significant islet mass may be destroyed upon infusion due to a yet undefined process known as instant blood-mediated inflammatory reaction (IBMIR). Our objective was to identify gene expression changes in islets undergoing a simulated process of IBMIR. Materials and Methods: Human pancreatic islets were isolated from 2 cadaveric donors and divided into 3 groups each for a total of 18 samples. Group one (n = 3) was treated with autologous sera, group two (n = 3) with allogeneic sera, and group three (n = 3) with type 1 diabetic sera (T1DM). Each group was treated for 3 hours at 37°C. Islets were washed, lysed using TRI reagent, and mRNA was isolated using the Total Prep mRNA isolation kit. Isolated cRNA was used for microarray analysis using Illumina Gene Chips Hu6_v2. GeneSpring GX software was used for statistical analysis. Results were significant at P < .05. Results: One-way ANOVA statistical analysis of the microarray data revealed that interleukin-11 (IL-11), interleukin-12A (IL-12A), and Ras related associated with diabetes (RRAD) were overexpressed in islets exposed to diabetic sera when normalized to autologous control (P < .01). Under the same conditions, islet cells exposed to T1DM serum had down-regulation of IL-1 receptor antagonist (IL-1RN). Conclusion: These findings suggested that T1DM serum elicited an adaptive and innate immune response to the transplanted islet mass making them more susceptible to cytokine-mediated destruction.
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U2 - 10.1016/j.transproceed.2008.01.021
DO - 10.1016/j.transproceed.2008.01.021
M3 - Article
C2 - 18374091
AN - SCOPUS:40949115087
SN - 0041-1345
VL - 40
SP - 430
EP - 432
JO - Transplantation proceedings
JF - Transplantation proceedings
IS - 2
ER -