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A Common Polymorphism in the Monocyte Chemoattractant Protein-1 (MCP-1) Gene Regulatory Region Influences MCP-1 Expression and Function of Isolated Human Pancreatic Islets

Del Guerra, S ; D'Aleo, V ; Gualtierotti, G ; Filipponi, F ; Boggi, U ; De Simone, P ; Vistoli, F ; Del Prato, S ; Marchetti, P ; Lupi, R

Transplantation proceedings, 2010-07, Vol.42 (6), p.2247-2249 [Periódico revisado por pares]

Amsterdam: Elsevier Inc

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Título:
A Common Polymorphism in the Monocyte Chemoattractant Protein-1 (MCP-1) Gene Regulatory Region Influences MCP-1 Expression and Function of Isolated Human Pancreatic Islets
Autor: Del Guerra, S ; D'Aleo, V ; Gualtierotti, G ; Filipponi, F ; Boggi, U ; De Simone, P ; Vistoli, F ; Del Prato, S ; Marchetti, P ; Lupi, R
Assuntos: Adenine - analysis ; Biological and medical sciences ; Chemokine CCL2 - genetics ; Diabetes Mellitus, Type 1 - surgery ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Gene Expression Regulation ; Glucose - pharmacology ; Guanine - analysis ; Humans ; Inflammation - etiology ; Inflammation - genetics ; Insulin - metabolism ; Insulin Secretion ; Islets of Langerhans - drug effects ; Islets of Langerhans - metabolism ; Islets of Langerhans - physiology ; Islets of Langerhans Transplantation - adverse effects ; Medical sciences ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Regulatory Sequences, Nucleic Acid - genetics ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; Surgery ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Tissue Donors ; Tissue, organ and graft immunology
É parte de: Transplantation proceedings, 2010-07, Vol.42 (6), p.2247-2249
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Descrição: Abstract Background and aims Islet transplantation is an attractive approach to treat type 1 diabetic patients. However, suboptimal islet engraftment still represents an unsolved problem. It has been shown that human islets release monocyte chemoattractant protein-1 (MCP-1), one of the most powerful macrophage chemokines, which may impair the fate of the transplant. The aim of this study was to evaluate the presence and role of MCP-1 in isolated human islets, including genotyping for a common polymorphism. Methods Pancreatic islets were isolated by enzymatic digestion and gradient purification from 41 nondiabetic multiorgan donors. We measured MCP-1 mRNA expression by quantitative real- time reverse-transcriptase polymerization chain reaction, analyzed the MCP-1 single nucleotide polymorphism, −2518 G/A (SNP, rs 1024611) and evaluated glucose-stimulated insulin release (IR; μU/islet/min). Results MCP-1 mRNA expression was found in all studied batches of islets. Overall, IR was significantly higher at 16.7 mmol/L than 3.3 mmol/L glucose. We observed a significant negative correlation between MCP-1 mRNA expression and stimulation index (SI). We found that MCP-1 mRNA expression was significantly higher in CC and CT compared with TT genotype groups. Finally, SI was significant lower in the CC with respect to the TT genotype group. Conclusions These data show that MCP-1 gene expression regulated by the −2518 G/A polymorphism, is correlated with glucose-stimulated insulin release. The study of MCP-1 expression and genotype on isolated islets before transplantation may be useful to understand the inflammatory response after infusion of human islets into patients with type 1 diabetes mellitus.
Editor: Amsterdam: Elsevier Inc
Idioma: Inglês

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A Common Polymorphism in the Monocyte Chemoattractant Protein-1 (MCP-1) Gene Regulatory Region Influences MCP-1 Expression and Function of Isolated Human Pancreatic Islets

Del Guerra, S ; D'Aleo, V ; Gualtierotti, G ; Filipponi, F ; Boggi, U ; De Simone, P ; Vistoli, F ; Del Prato, S ; Marchetti, P ; Lupi, R

Amsterdam: Elsevier Inc

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