Alpha cells, the main source of IL-1β in human pancreas

被引:28
作者
Anquetil, Florence [1 ]
Sabouri, Somayeh [1 ]
Thivolet, Charles [1 ]
Rodriguez-Calvo, Teresa [1 ]
Zapardiel-Gonzalo, Jose [1 ]
Amirian, Natalie [1 ]
Schneider, Darius [1 ]
Castillo, Ericka [1 ]
Lajevardi, Yasaman [1 ]
von Herrath, Matthias G. [1 ,2 ]
机构
[1] La Jolla Inst Allergy & Immunol, Type Diabet Ctr 1, La Jolla, CA USA
[2] Novo Nordisk Diabet Res & Dev Ctr, Seattle, WA USA
基金
美国国家卫生研究院;
关键词
Alpha cells; Interleukin-1; beta; Type; 1; diabetes; Pancreas; DIABETES-MELLITUS; RECEPTOR ANTAGONIST; HUMAN ISLETS; BETA-CELLS; INTERLEUKIN-1; GLUCOSE; RAT; EXPRESSION; THERAPY; RELEASE;
D O I
10.1016/j.jaut.2017.03.006
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Interleukin-1 beta (IL-1 beta) is known to trigger beta cell dysfunction in vitro and could potentially play a role during the pathogenesis of type 1 diabetes and type 2 diabetes. However, several clinical trials attempting to block IL-1 beta function have had minimal success. We therefore re-investigated local expression of IL-1 beta in human diabetic and non-diabetic pancreata. We obtained pancreatic tissue sections from the Network for Pancreatic Organ Donors with Diabetes (nPOD) including non-diabetic (n = 9), non-diabetic auto-antibody positive (AAb+, n = 5), type I diabetes (n = 6), and type 2 diabetes (n = 6) donors. Islets were systematically investigated for the presence of IL-1 beta mRNA by in situ hybridization and IL-1 beta protein by indirect immunofluorescence. We found that intra-islet IL-1 beta was produced at comparable level in both non-diabetic and diabetic donors. Interestingly, the main source for IL-1 beta was alpha cells but not beta cells. Our findings call into question the role of IL-1 beta in the diabetic pancreas as it has been proposed in previous literature. Additionally, our results regarding the localization of IL-1 beta should lead to further investigation into the role of IL-1 beta in the physiology of pancreatic alpha cells. (C) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码:68 / 73
页数:6
相关论文
共 28 条
[1]   Antidiabetic Effect of Interleukin-1β Antibody Therapy Through β-Cell Protection in the Cohen Diabetes-Sensitive Rat [J].
Aharon-Hananel, Genya ;
Joerns, Anne ;
Lenzen, Sigurd ;
Raz, Itamar ;
Weksler-Zangen, Sarah .
DIABETES, 2015, 64 (05) :1780-1785
[2]   Genetic polymorphisms of cytokine genes in type 2 diabetes mellitus [J].
Banerjee, Monisha ;
Saxena, Madhukar .
WORLD JOURNAL OF DIABETES, 2014, 5 (04) :493-504
[3]   SOCS-1 protects from virally-induced CD8 T cell mediated type 1 diabetes [J].
Barral, Ana Maria ;
Thomas, Helen E. ;
Ling, Eleanor M. ;
Darwiche, Rima ;
Rodrigo, Evelyn ;
Christen, Urs ;
Ejrnaes, Mette ;
Wolfe, Tom ;
Kay, Thomas W. ;
von Herrath, Matthias G. .
JOURNAL OF AUTOIMMUNITY, 2006, 27 (03) :166-173
[4]   Free Fatty Acids Induce a Proinflammatory Response in Islets via the Abundantly Expressed Interleukin-1 Receptor I [J].
Boeni-Schnetzler, Marianne ;
Boller, Simone ;
Debray, Sarah ;
Bouzakri, Karim ;
Meier, Daniel T. ;
Prazak, Richard ;
Kerr-Conte, Julie ;
Pattou, Francois ;
Ehses, Jan A. ;
Schuit, Frans C. ;
Donath, Marc Y. .
ENDOCRINOLOGY, 2009, 150 (12) :5218-5229
[5]   Increased interleukin (IL)-1β messenger ribonucleic acid expression in β-cells of individuals with type 2 diabetes and regulation of IL-1β in human islets by glucose and autostimulation [J].
Boni-Schnetzler, Marianne ;
Thorne, Jeffrey ;
Parnaud, Geraldine ;
Marselli, Lorella ;
Ehses, Jan A. ;
Kerr-Conte, Julie ;
Pattou, Francois ;
Halban, Philippe A. ;
Weir, Gordon C. ;
Donath, Marc Y. .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2008, 93 (10) :4065-4074
[6]   Role of IL-1β in type 2 diabetes [J].
Dinarello, Charles A. ;
Donath, Marc Y. ;
Mandrup-Poulsen, Thomas .
CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY, 2010, 17 (04) :314-321
[7]   Cytokine production by islets in health and diabetes: cellular origin, regulation and function [J].
Donath, Marc Y. ;
Boeni-Schnetzler, Marianne ;
Ellingsgaard, Helga ;
Halban, Philippe A. ;
Ehses, Jan A. .
TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2010, 21 (05) :261-267
[8]   Transcriptomes of the major human pancreatic cell types [J].
Dorrell, C. ;
Schug, J. ;
Lin, C. F. ;
Canaday, P. S. ;
Fox, A. J. ;
Smirnova, O. ;
Bonnah, R. ;
Streeter, P. R. ;
Stoeckert, C. J., Jr. ;
Kaestner, K. H. ;
Grompe, M. .
DIABETOLOGIA, 2011, 54 (11) :2832-2844
[9]   The Human Pancreatic Islet Transcriptome: Expression of Candidate Genes for Type 1 Diabetes and the Impact of Pro-Inflammatory Cytokines [J].
Eizirik, Decio L. ;
Sammeth, Michael ;
Bouckenooghe, Thomas ;
Bottu, Guy ;
Sisino, Giorgia ;
Igoillo-Esteve, Mariana ;
Ortis, Fernanda ;
Santin, Izortze ;
Colli, Maikel L. ;
Barthson, Jenny ;
Bouwens, Luc ;
Hughes, Linda ;
Gregory, Lorna ;
Lunter, Gerton ;
Marselli, Lorella ;
Marchetti, Piero ;
McCarthy, Mark I. ;
Cnop, Miriam .
PLOS GENETICS, 2012, 8 (03)
[10]  
Kay T.W., 2008, NOVART FDN SYMP, V292, P202