Hyaluronan oligosaccharides induce inflammatory response in human thyrocytes cultures by affecting Toll-like receptors

Autoimmune Thyroid diseases, such as Hashimoto’s thyroidite, result in characteristic lymphocytic infiltration and altered function of the thyroid. During inflammation, cytokines increase hyaluronan (HA) production that accumulates in the thyroid (1).
Hyaluronan (HA) fragments produced in different pathological states can modulate gene expression in a variety of cell types and may prime inflammatory response by interacting with the Toll-like receptor 2 (TLR-2), Toll-like receptor 4 (TLR-4) and CD44 (2, 3). Particularly, TLRs activation induces a signaling complex mediated by adapter molecules, such as myeloid differentiation primary response (MyD88) and tumor necrosis factor receptor associated factor 6 (TRAF-6), that culminates in the nuclear factor kappaB (NF-kB) activation. NF-kB in turn modulates the expression of inflammation mediators, as inteleukin-1beta (IL-1beta) and inteleukin-6 (IL-6).
The aim of this study was to investigate the effect of 6-mer HA oligosaccharides on human thyrocytes. HA treatment induced up-regulation of TLR-2, TLR-4, MyD88 and TRAF-6 mRNA expression and related protein levels, and NF-kB activation that in turn increased IL-1beta and IL-6 concentrations. The exposure of thyrocytes to two specific blocking antibodies for TLR-2 and TLR-4 abolished up-regulation of MyD88 and TRAF-6, and significantly reduced NF-κB activation and pro-inflammatory cytokine production.
This data suggest that HA depolymerization occurring during inflammation may contribute to prime the inflammatory response in thyrocytes through activation of TLR-2 and TLR-4 signalling cascade.