Deletion of 12/15-lipoxygenase alters macrophage and islet function in NOD-Alox15(null) mice, leading to protection against type 1 diabetes development.

<h4>Aims</h4>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,...

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Autores principales:	Shamina M Green-Mitchell, Sarah A Tersey, Banumathi K Cole, Kaiwen Ma, Norine S Kuhn, Tina Duong Cunningham, Nelly A Maybee, Swarup K Chakrabarti, Marcia McDuffie, David A Taylor-Fishwick, Raghavendra G Mirmira, Jerry L Nadler, Margaret A Morris
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1f42c924931446b8bba73f20a5d64368
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spelling	oai:doaj.org-article:1f42c924931446b8bba73f20a5d643682021-11-18T07:56:35ZDeletion of 12/15-lipoxygenase alters macrophage and islet function in NOD-Alox15(null) mice, leading to protection against type 1 diabetes development.1932-620310.1371/journal.pone.0056763https://doaj.org/article/1f42c924931446b8bba73f20a5d643682013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23437231/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Aims</h4>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.<h4>Methods</h4>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-Alox15(null) 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.<h4>Results</h4>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-Alox15(null) 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.<h4>Conclusions</h4>These results suggest that 12/15-LO affects islet and macrophage function, causing inflammation, and leading to autoimmunity and reduced beta cell mass.Shamina M Green-MitchellSarah A TerseyBanumathi K ColeKaiwen MaNorine S KuhnTina Duong CunninghamNelly A MaybeeSwarup K ChakrabartiMarcia McDuffieDavid A Taylor-FishwickRaghavendra G MirmiraJerry L NadlerMargaret A MorrisPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e56763 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shamina M Green-Mitchell Sarah A Tersey Banumathi K Cole Kaiwen Ma Norine S Kuhn Tina Duong Cunningham Nelly A Maybee Swarup K Chakrabarti Marcia McDuffie David A Taylor-Fishwick Raghavendra G Mirmira Jerry L Nadler Margaret A Morris Deletion of 12/15-lipoxygenase alters macrophage and islet function in NOD-Alox15(null) mice, leading to protection against type 1 diabetes development.
description	<h4>Aims</h4>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.<h4>Methods</h4>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-Alox15(null) 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.<h4>Results</h4>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-Alox15(null) 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.<h4>Conclusions</h4>These results suggest that 12/15-LO affects islet and macrophage function, causing inflammation, and leading to autoimmunity and reduced beta cell mass.
format	article
author	Shamina M Green-Mitchell Sarah A Tersey Banumathi K Cole Kaiwen Ma Norine S Kuhn Tina Duong Cunningham Nelly A Maybee Swarup K Chakrabarti Marcia McDuffie David A Taylor-Fishwick Raghavendra G Mirmira Jerry L Nadler Margaret A Morris
author_facet	Shamina M Green-Mitchell Sarah A Tersey Banumathi K Cole Kaiwen Ma Norine S Kuhn Tina Duong Cunningham Nelly A Maybee Swarup K Chakrabarti Marcia McDuffie David A Taylor-Fishwick Raghavendra G Mirmira Jerry L Nadler Margaret A Morris
author_sort	Shamina M Green-Mitchell
title	Deletion of 12/15-lipoxygenase alters macrophage and islet function in NOD-Alox15(null) mice, leading to protection against type 1 diabetes development.
title_short	Deletion of 12/15-lipoxygenase alters macrophage and islet function in NOD-Alox15(null) mice, leading to protection against type 1 diabetes development.
title_full	Deletion of 12/15-lipoxygenase alters macrophage and islet function in NOD-Alox15(null) mice, leading to protection against type 1 diabetes development.
title_fullStr	Deletion of 12/15-lipoxygenase alters macrophage and islet function in NOD-Alox15(null) mice, leading to protection against type 1 diabetes development.
title_full_unstemmed	Deletion of 12/15-lipoxygenase alters macrophage and islet function in NOD-Alox15(null) mice, leading to protection against type 1 diabetes development.
title_sort	deletion of 12/15-lipoxygenase alters macrophage and islet function in nod-alox15(null) mice, leading to protection against type 1 diabetes development.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/1f42c924931446b8bba73f20a5d64368
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Deletion of 12/15-lipoxygenase alters macrophage and islet function in NOD-Alox15(null) mice, leading to protection against type 1 diabetes development.

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