Nitric Oxide Is a Mediator of Antiproliferative Effects Induced by Proinflammatory Cytokines on Pancreatic Beta Cells
| Autor: | Carmen Segundo, Gonzalo Perez-Arana, Alfonso M. Lechuga-Sancho, Laura Quintana-Lopez, Manuel Aguilar-Diosdado, Alberto Cebada-Aleu, Manuel Blandino-Rosano |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Article Subject Blotting Western Interleukin-1beta Immunology Fluorescent Antibody Technique Nitric Oxide Proinflammatory cytokine Nitric oxide Interferon-gamma chemistry.chemical_compound Insulin-Secreting Cells Internal medicine lcsh:Pathology medicine Animals Nitric Oxide Donors Rats Wistar Cell Proliferation omega-N-Methylarginine biology Tumor Necrosis Factor-alpha Pancreatic islets Body Weight Cell Biology medicine.disease Rats Nitric oxide synthase Endocrinology medicine.anatomical_structure chemistry Guanylate Cyclase Apoptosis biology.protein Cancer research Cytokines Omega-N-Methylarginine Tumor necrosis factor alpha Nitric Oxide Synthase Insulitis lcsh:RB1-214 Research Article |
| Zdroj: | Mediators of Inflammation Mediators of Inflammation, Vol 2013 (2013) |
| ISSN: | 0962-9351 |
| DOI: | 10.1155/2013/905175 |
| Popis: | Nitric oxide (NO) is involved in several biological processes. In type 1 diabetes mellitus (T1DM), proinflammatory cytokines activate an inducible isoform of NOS (iNOS) inβcells, thus increasing NO levels and inducing apoptosis. The aim of the current study is to determine the role of NO (1) in the antiproliferative effect of proinflammatory cytokines IL-1β, IFN-γ, and TNF-αon cultured isletβcells and (2) during the insulitis stage prior to diabetes onset using the Biobreeding (BB) rat strain as T1DM model. Our results indicate that NO donors exert an antiproliferative effect onβcell obtained from cultured pancreatic islets, similar to that induced by proinflammatory cytokines. This cytokine-induced antiproliferative effect can be reversed by L-NMMA, a general NOS inhibitor, and is independent of guanylate cyclase pathway. Assays using NOS isoform specific inhibitors suggest that the NO implicated in the antiproliferative effect of proinflammatory cytokines is produced by inducible NOS, although not in an exclusive way. In BB rats, early treatment with L-NMMA improves the initial stage of insulitis. We conclude that NO is an important mediator of antiproliferative effect induced by proinflammatory cytokines on culturedβcell and is implicated inβ-cell proliferation impairment observed early from initial stage of insulitis. |
| Databáze: | OpenAIRE |
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