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Expression of the NK-1 receptor on islet cells and invading immune cells in the non-obese diabetic mouse
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
2005 (English)In: Journal of Autoimmunity, ISSN 0896-8411, Vol. 24, no 4, 269-279 p.Article in journal (Refereed) Published
Abstract [en]

The underlying mechanistic causes of immune cell infiltration in the islets of Langerhans and beta cell failure in the non-obese diabetic (NOD) mouse is still to be completely revealed. Substance P (SP) is a substance known to have pro-inflammatory, endocrine, neuromodulatory and trophic effects, and its preferred receptor, the neurokinin receptor 1 (NK-1 R), is reported to be involved in extravasation of granulocytes and in inflammation and tissue derangement. Therefore, we have investigated the expression of NK-1 R during development of insulitis in the NOD mouse. We show that the magnitude of immunoreactivity scoring NK-1 R expression in the islets was increased in the 12-week-old NOD mouse. Expression of NK-1 R co-localized with expression of glucagon. In line with this expression pattern, we did not detect any effect of SP on glucose-induced insulin release. NK-1 R expression was particularly observed in islet cells in association with the clusters of immune cells. Expression of NK-1 R was also demonstrated in a fraction of the infiltrating B and T lymphocytes, as well as on infiltrating macrophages and dendritic cells. The observations show that the level of NK-1 R expression is increased in 12-week-old NOD mice, being correlated with the occurrence of islet mononuclear infiltration. Our data suggest that SP may act as a chemoattractant, contributing to the pathogenic mononuclear infiltration process in the NOD mouse. On the whole, the observations suggest that SP and the NK-1 R to certain extents are involved in the changes that occur during the development of insulitis in the NOD mouse.

Place, publisher, year, edition, pages
Elsevier, 2005. Vol. 24, no 4, 269-279 p.
Keyword [en]
Animals, Diabetes Mellitus; Type 1/immunology/pathology, Gene Expression Regulation/*immunology, Islets of Langerhans/*immunology/pathology, Leukocytes/*immunology/pathology, Mice, Mice; Inbred NOD, Receptors; Neurokinin-1/*biosynthesis/immunology, Substance P/immunology
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:umu:diva-12699DOI: 10.1016/j.jaut.2005.02.003PubMedID: 15869864OAI: oai:DiVA.org:umu-12699DiVA: diva2:152370
Available from: 2008-01-11 Created: 2008-01-11 Last updated: 2014-04-11Bibliographically approved

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Persson-Sjögren, SolveigLejon, KristinaHolmberg, DanForsgren, Sture

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