Low molecular weight HA elicited pro-inflammatory responses by modulating both toll-like receptor 4 (TLR-4) and CD44. CD44 and TLR-4 stimulation activates different inflammatory pathways that culminate with the activation of the transcriptional nuclear factor kappaB (NF-kappaB), which in turn is responsible for the expression of inflammation mediators such as tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1 beta (IL-1beta), [1,2]. Although, the pro- inflammatory effects of HA small fragments have been reported in several cell lines such as fibroblasts, chondrocytes and synoviocytes [2,3], little is known about such effects in neuronal cells. The aim of this study was to investigate the influence of short HA oligosaccharides (HA 6-mers) in the inflammatory response in neuronal-like differentiated SH-SY5Y neuroblastoma cells. mRNA and related protein levels were measured for: TLR-2, TLR-4, CD44, TNF-alpha, iNOS, IL-1beta, IL-6, and the matrix metalloprotease-2 and 9 (MMP-2 and MMP-9) in cells with and without the addition of HA 6mer. NF-kB activation was also evaluated. 6-mer HA treatment produced a significant up-regulation of all parameters considered, which is in line with the well-known pro inflammatory effect of low molecular weight HA. Experiments using small interfering RNAs (siRNAs) are in progress, with the aim to block TLR-2, TLR-4 and CD44 expression. The modulatory effects of such experiments will be discussed. 1.Campo GM et al. Arch Biochem Biophys. 2012, 518:42-52. 2. Campo GM et al. Biochem Pharmacol. 2010, 80:480-90. 3. Campo GM et al. Innate Immun. 2012,18: 675-684.
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