Autoimmune thyroid diseases, such as Hashimoto's thyroiditis, are characterized by lymphocytic infiltration and altered function of the thyroid. During inflammation, it has been reported a decreased expression in Tg and NIS, accompanied by an increase in HA production that accumulates in the gland.

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 TLR-2, TLR-4 and CD44 that, in turn, induce NF-kB activation finally responsible of inflammatory mediator transcription, such as IL-1β, TNF-α and IL-6.

The aim of this study was to investigate the potential inflammatory effect and the biochemical pathways activated by 6-mer HA oligosaccharides in cultured human thyrocytes. 6-mer HA treatment induced up-regulation of TLR-2, TLR-4, CD44 mRNA and related protein levels, increased HA production and NF-kB activation, that in turn increased IL-1β and IL-6 concentrations. Instead, we found evidence of an opposite effect on thyroid specific-gene Tg and NIS, that were decreased after 6-mer HA addition. Thyrocytes exposition to specific blocking antibodies for TLR-2, TLR-4 and CD44 abolished up-regulation of NF-κB activation and the consequent pro-inflammatory cytokine production, while restored Tg and NIS levels. A further goal of this study was demonstrate that also other LMW HA have pro inflammatory proprieties.

These data suggest that HA fragments, through the involvement of TLR-2, TLR-4 and CD44 signaling cascade, contribute to prime the inflammatory response in thyrocytes and, by reducing the expression of thyroid-specific genes, could promote the loss of function of gland such as in Hashimoto's thyroiditis.

自身免疫性甲状腺疾病（例如桥本氏甲状腺炎）的特征是淋巴细胞浸润和甲状腺功能改变。据报道，在炎症过程中，Tg和NIS的表达下降，伴随着腺体中HA产生的增加。

在不同病理状态下产生的HA片段可以调节多种细胞类型中的基因表达，并可能通过与TLR-2，TLR-4和CD44相互作用引发炎症反应，进而诱导NF-kB活化，最终引起炎症介质转录，例如IL-1β，TNF-α和IL-6。

这项研究的目的是调查潜在的炎症作用和培养的人甲状腺细胞中6-mer HA寡糖激活的生化途径。6-mer HA处理可诱导TLR-2，TLR-4，CD44 mRNA和相关蛋白水平上调，HA产量增加和NF-kB激活，进而增加IL-1β和IL-6的浓度。相反，我们发现了对甲状腺特异性基因Tg和NIS具有相反作用的证据，添加6-mer HA后这些作用减弱。胸腺细胞暴露于针对TLR-2，TLR-4和CD44的特异性阻断抗体，从而消除了NF-κB激活的上调和随之而来的促炎性细胞因子的产生，同时恢复了Tg和NIS的水平。这项研究的另一个目标是证明其他LMW HA也具有促炎作用。

这些数据表明，HA片段通过TLR-2，TLR-4和CD44信号级联反应的参与，有助于引发甲状腺细胞的炎症反应，并且通过减少甲状腺特异性基因的表达，可以促进甲状腺功能的丧失。桥本甲状腺炎等腺体。