Changes in expression of IL-1� influenced proteins in transplanted islets during development of diabetes in diabetes-prone BB rats

Sparre, Thomas; Bjerre-Christensen, Ulla; Gotfredsen, Carsten F.; Larsen, Peter Mose; Fey, Stephen J.; Hjernø, K.; Roepstorff, Peter; Pociot, Flemming; Karlsen, Allan E.; Nerup, Jørn

doi:10.1007/s00125-004-1382-y

Cited by 23 publications

(1 citation statement)

References 69 publications

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“…The development and chronicity of several autoimmune diseases (systemic lupus erythematosus (SEL), primary Sjögren's syndrome, thyroid autoimmunity, type I diabetes (T1D), and rheumatoid arthritis (RA)) are associated with a constant synthesis of IL-1β [55,56]. This cytokine affects cell survival by decreasing the DNA content and reducing protein synthesis, metabolism, energy production, and the cell cycle, thus favoring the development of autoimmune disorders [57]. For example, elevated serum levels of IL-1β along with those of TNF-α have been associated with increased pancreatic β-cell destruction in patients with T1D, at all stages of the disease [58][59][60][61][62].…”

Section: The Non-polar Extract and The More Polar Fractions Obtained ...mentioning

confidence: 99%

A Bidens pilosa L. Non-Polar Extract Modulates the Polarization of Human Macrophages and Dendritic Cells into an Anti-Inflammatory Phenotype

Rodríguez Mesa,

Contreras Bolaños,

Modesti Costa

et al. 2023

Molecules

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Different communities around the world traditionally use Bidens pilosa L. for medicinal purposes, mainly for its anti-inflammatory, antinociceptive, and antioxidant properties; it is used as an ingredient in teas or herbal medicines for the treatment of pain, inflammation, and immunological disorders. Several studies have been conducted that prove the immunomodulatory properties of this plant; however, it is not known whether the immunomodulatory properties of B. pilosa are mediated by its ability to modulate antigen-presenting cells (APCs) such as macrophages (MØs) and dendritic cells (DCs) (through polarization or the maturation state, respectively). Different polar and non-polar extracts and fractions were prepared from the aerial part of B. pilosa. Their cytotoxic and immunomodulatory effects were first tested on human peripheral blood mononuclear cells (PBMCs) and phytohemagglutinin (PHA)-stimulated PBMCs, respectively, via an MTT assay. Then, the non-cytotoxic plant extracts and fractions that showed the highest immunomodulatory activity were selected to evaluate their effects on human MØ polarization and DC maturation (cell surface phenotype and cytokine secretion) through multiparametric flow cytometry. Finally, the chemical compounds of the B. pilosa extract that showed the most significant immunomodulatory effects on human APCs were identified using gas chromatography coupled with mass spectrometry. The petroleum ether extract and the ethyl acetate and hydroalcoholic fractions obtained from B. pilosa showed low cytotoxicity and modulated the PHA-stimulated proliferation of PBMCs. Furthermore, the B. pilosa petroleum ether extract induced M2 polarization or a hybrid M1/M2 phenotype in MØs and a semi-mature status in DCs, regardless of exposure to a maturation stimulus. The immunomodulatory activity of the non-polar (petroleum ether) extract of B. pilosa on human PBMC proliferation, M2 polarization of MØs, and semi-mature status in DCs might be attributed to the low–medium polarity components in the extract, such as phytosterol terpenes and fatty acid esters.

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Section: The Non-polar Extract and The More Polar Fractions Obtained ...mentioning

confidence: 99%

A Bidens pilosa L. Non-Polar Extract Modulates the Polarization of Human Macrophages and Dendritic Cells into an Anti-Inflammatory Phenotype

Rodríguez Mesa,

Contreras Bolaños,

Modesti Costa

et al. 2023

Molecules

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Current literature in diabetes

2005

Diabetes Metab. Res. Rev.

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Galectin‐3 deficiency protects pancreatic islet cells from cytokine‐triggered apoptosis in vitro

Saksida

Nikolić

Vujičić

et al. 2013

Journal Cellular Physiology

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Beta cell apoptosis is a hallmark of diabetes. Since we have previously shown that galectin-3 deficient (LGALS3(-/-) ) mice are relatively resistant to diabetes induction, the aim of this study was to examine whether beta cell apoptosis depends on the presence of galectin-3 and to delineate the underlying mechanism. Deficiency of galectin-3, either hereditary or induced through application of chemical inhibitors, β-lactose or TD139, supported survival and function of islet beta cells compromised by TNF-α + IFN-γ + IL-1β stimulus. Similarly, inhibition of galectin-3 by β-lactose or TD139 reduced cytokine-triggered apoptosis of beta cells, leading to conclusion that endogenous galectin-3 propagates beta apoptosis in the presence of an inflammatory milieu. Exploring apoptosis-related molecules expression in primary islet cells before and after treatment with cytokines we found that galectin-3 ablation affected the expression of major components of mitochondrial apoptotic pathway, such as BAX, caspase-9, Apaf, SMAC, caspase-3, and AIF. In contrast, anti-apoptotic molecules Bcl-2 and Bcl-XL were up-regulated in LGALS3(-/-) islet cells when compared to wild-type (WT) counterparts (C57BL/6), resulting in increased ratio of anti-apoptotic versus pro-apoptotic molecules. However, Fas-triggered apoptotic pathway as well as extracellular signal-regulated kinase 1/2 (ERK1/2) was not influenced by LGALS-3 deletion. All together, these results point to an important role of endogenous galectin-3 in beta cell apoptosis in the inflammatory milieu that occurs during diabetes pathogenesis and implicates impairment of mitochondrial apoptotic pathway as a key event in protection from beta cell apoptosis in the absence of galectin-3.

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Changes in expression of IL-1� influenced proteins in transplanted islets during development of diabetes in diabetes-prone BB rats

Cited by 23 publications

References 69 publications

A Bidens pilosa L. Non-Polar Extract Modulates the Polarization of Human Macrophages and Dendritic Cells into an Anti-Inflammatory Phenotype

A Bidens pilosa L. Non-Polar Extract Modulates the Polarization of Human Macrophages and Dendritic Cells into an Anti-Inflammatory Phenotype

Current literature in diabetes

Galectin‐3 deficiency protects pancreatic islet cells from cytokine‐triggered apoptosis in vitro

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