التفاصيل البيبلوغرافية
| العنوان: |
Deletion of 12/15-Lipoxygenase Alters Macrophage and Islet Function in NOD-Alox15null Mice, Leading to Protection against Type 1 Diabetes Development. |
| المؤلفون: |
Green-Mitchell, Shamina M., Tersey, Sarah A., Cole, Banumathi K., Ma, Kaiwen, Kuhn, Norine S., Cunningham, Tina Duong, Maybee, Nelly A., Chakrabarti, Swarup K., McDuffie, Marcia, Taylor-Fishwick, David A., Mirmira, Raghavendra G., Nadler, Jerry L., Morris, Margaret A. |
| المصدر: |
PLoS ONE; Feb2013, Vol. 8 Issue 2, p1-11, 11p |
| مصطلحات موضوعية: |
LIPOXYGENASES, MACROPHAGES, ISLANDS of Langerhans, TYPE 1 diabetes, PANCREATIC beta cells, AUTOIMMUNE diseases, MOLECULAR biology, LABORATORY mice |
| مستخلص: |
Aims: Type 1 diabetes (T1D) is characterized by autoimmune depletion of insulin-producing pancreatic beta cells. We showed previously that deletion of the 12/15-lipoxygenase enzyme (12/15-LO, Alox15 gene) in NOD mice leads to nearly 100 percent protection from T1D. In this study, we test the hypothesis that cytokines involved in the IL-12/12/15-LO axis affect both macrophage and islet function, which contributes to the development of T1D. Methods: 12/15-LO expression was clarified in immune cells by qRT-PCR, and timing of expression was tested in islets using qRT-PCR and Western blotting. Expression of key proinflammatory cytokines and pancreatic transcription factors was studied in NOD and NOD-Alox15null macrophages and islets using qRT-PCR. The two mouse strains were also assessed for the ability of splenocytes to transfer diabetes in an adoptive transfer model, and beta cell mass. Results: 12/15-LO is expressed in macrophages, but not B and T cells of NOD mice. In macrophages, 12/15-LO deletion leads to decreased proinflammatory cytokine mRNA and protein levels. Furthermore, splenocytes from NOD-Alox15null mice are unable to transfer diabetes in an adoptive transfer model. In islets, expression of 12/15-LO in NOD mice peaks at a crucial time during insulitis development. The absence of 12/15-LO results in maintenance of islet health with respect to measurements of islet-specific transcription factors, markers of islet health, proinflammatory cytokines, and beta cell mass. Conclusions: These results suggest that 12/15-LO affects islet and macrophage function, causing inflammation, and leading to autoimmunity and reduced beta cell mass. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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