Interleukin-18 alters protein expressions of neurodegenerative diseases-linked proteins in human SH-SY5Y neuron-like cells

• Published in: Frontiers in cellular neuroscience 2014-08, Vol.8, p.214-214
• Main Authors: Sutinen, Elina M, Korolainen, Minna A, Häyrinen, Jukka, Alafuzoff, Irina, Petratos, Steven, Salminen, Antero, Soininen, Hilkka, Pirttilä, Tuula, Ojala, Johanna O
• Format: Article
• Language: English
• Subjects: 14-3-3; Alzheimer's disease; Amyloid; Apoptosis; Brain research; Caspase; Caspase-1; Cell differentiation; CRMP2; Cyclin-dependent kinase 5; Cytokines; DDAH; Diabetes; Diabetes mellitus; Dimethylargininase; Gel electrophoresis; Glycolysis; Immunoblotting; Inflammation; Interleukin 18; Kinases; Labeling; Laboratories; Mass Spectrometry; Mass spectroscopy; Mediator protein; Medical research; MMP14; Nervous system; Neurodegenerative diseases; Neurofibrillary tangles; Neuropathology; Neuroscience; Oxidative stress; oxidative stress related proteins; PARK7 protein; Pathology; Phosphopyruvate hydratase; Phosphorylation; Proteins; Proteomes; Proteomics; Rho-associated kinase; Senile plaques; Septin
• ISSN: 1662-5102; 1662-5102
• DOI: 10.3389/fncel.2014.00214

Chronic inflammation and oxidative stress (OS) are present in Alzheimer's disease (AD) brains in addition to neuronal loss, Amyloid-β (Aβ) plaques and hyperphosphorylated tau-protein neurofibrillary tangles (NFTs). Previously we showed that levels of the pro-inflammatory cytokine, interleukin-18 (IL-18), are elevated in post-mortem AD brains. IL-18 can modulate the tau kinases, Cdk5 and GSK3β, as well as Aβ-production. IL-18 levels are also increased in AD risk diseases, including type-2 diabetes and obesity. Here, we explored other IL-18 regulated proteins in neuron-like SH-SY5Y cells. Differentiated SH-SY5Y cells, incubated with IL-18 for 24, 48, or 72 h, were analyzed by two-dimensional gel electrophoresis (2D-DIGE). Specific altered protein spots were chosen and identified with mass spectrometry (MS) and verified by western immunoblotting (WIB). IL-18 had time-dependent effects on the SH-SY5Y proteome, modulating numerous protein levels/modifications. We concentrated on those related to OS (DDAH2, peroxiredoxins 2, 3, and 6, DJ-1, BLVRA), Aβ-degradation (MMP14, TIMP2), Aβ-aggregation (Septin-2), and modifications of axon growth and guidance associated, collapsin response mediator protein 2 (CRMP2). IL-18 significantly increased antioxidative enzymes, indicative of OS, and altered levels of glycolytic α- and γ-enolase and multifunctional 14-3-3γ and -ε, commonly affected in neurodegenerative diseases. MMP14, TIMP2, α-enolase and 14-3-3ε, indirectly involved in Aβ metabolism, as well as Septin-2 showed changes that increase Aβ levels. Increased 14-3-3γ may contribute to GSK3β driven tau hyperphosphorylation and CRMP2 Thr514 and Ser522 phosphorylation with the Thr555-site, a target for Rho kinase, showing time-dependent changes. IL-18 also increased caspase-1 levels and vacuolization of the cells. Although our SH-SY5Y cells were not aged, as neurons in AD, our work suggests that heightened or prolonged IL-18 levels can drive protein changes of known relevance to AD pathogenesis.