Hyaluronan oligosaccharides down-regulate NIS and thyroglobulin expression in human thyrocytes

Hashimoto’s thyroiditis is an autoimmune disease characterized by chronic inflammation and altered function of the thyroid, including hyaluronan (HA) accumulation. During inflammation HA can be degraded into small fragments that, by stimulating the TLR-2, TLR-4 and CD44 receptors, modulate inflammation in a NF-κB dependent manner. Evidences have shown that exists a correlation between inflammatory state and downregulation of thyroglobulin and sodium iodide symporter (NIS), the transporter that mediates the first step in thyroid hormone biosynthesis. In light of these findings, firstly we evaluated the pro-inflammatory effect of 6-mer HA oligosaccharides on primary human thyrocyte cultures; then we studied the effects of HA induced inflammation on the expression of thyroglobulin and NIS. Following 6-mer HA treatment IL-1β and IL-6 concentrations were increased, while thyroglobulin and NIS expression was decreased. On the contrary, the blockage of HA receptors reduced inflammatory mediator production, while thyroglobulin and NIS levels were restored. These data suggest a possible role of HA induced inflammation in the reduction of iodide transport and thyroid hormone biosynthesis.