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J Cell Biochem ; 117(12): 2835-2843, 2016 12.
Article in English | MEDLINE | ID: mdl-27167053

ABSTRACT

Several studies have shown the degradation of the extracellular matrix at the site of neuroinflammation and increased release of degradation products of glycosaminoglycans. Among these, low molecular weight fragments of hyaluronan (HA) may play a key role in the events leading to neuroinflammation and/or neuronal degeneration. Small HA fragments are able to induce inflammation by stimulating both TLR-2 and TLR-4 as well as CD44 receptors. This stimulation culminates in the nuclear translocation of NF-kB that in turn induces the production of pro-inflammatory intermediates such as TNF-α and IL-1ß. The potential of HA fragments, as mediators of inflammation, it has been poorly investigated in neuron-like SH-SY5Y cells so the aim of this study was to investigate the neuroinflammatory effects of very small HA oligosaccharides, the involvement of TLR-2, TLR-4, and CD44 and the production of α-synuclein in such cells. The addition of HA fragments to cell cultures up-regulated TLR-2, TLR-4, and CD44 levels, induced NF-kB activity and increased both TNF-α and IL-ß as well as α-synuclein production. On blocking the activity of TLR-2, TLR-4, and CD44 the levels of inflammatory parameters and of α-synuclein were significantly reduced. Since several data have shown as α-synuclein, produced from neurons, is able to initiate ex novo or to maintain an existing neuroinflammatory response, which has been suggested as one of the principal components involved in neurodegenerative pathologies, as PD, we suggest that HA pathways should be given careful consideration when devising future anti-neuroinflammatory strategies to defend against the onset of neurodegenerative disorders. J. Cell. Biochem. 117: 2835-2843, 2016. © 2016 Wiley Periodicals, Inc.


Subject(s)
Gene Expression Regulation, Neoplastic/drug effects , Hyaluronic Acid/pharmacology , Inflammation/pathology , Neuroblastoma/metabolism , Neuroblastoma/pathology , Oligosaccharides/pharmacology , alpha-Synuclein/metabolism , Adjuvants, Immunologic/chemistry , Adjuvants, Immunologic/pharmacology , Apoptosis/drug effects , Blotting, Western , Cell Proliferation/drug effects , Humans , Hyaluronic Acid/chemistry , Inflammation/drug therapy , Inflammation/metabolism , Neuroblastoma/drug therapy , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured , alpha-Synuclein/genetics
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