Lipopolysaccharide (LPS) elicits several immediate proinflammatory responses in peripheral blood leukocytes via Toll-like receptor 4 (TLR4). However, this cell wall compound of gram-negative bacteria induces the expression of different genes in numerous cell types. We previously demonstrated the functional expression of the LPS receptor, TLR4 and the accessory molecules CD14 and MD2 at the plasma membrane in the FRTL-5 rat thyroid cell line. In these cells LPS induced up-regulation of thyroglobulin and Na+/I- symporter gene expression. Increasing evidence indicates that chronical inflammatory processes that may lead to tumorigenesis are mediated in part through recognition of stimulus by TLR4.
This study aimed to analyze the action of LPS on thyroid cell proliferation in FRTL-5. We revealed that LPS increased the cell proliferation rate when measured by dilution of the intracelullar dye CFSE and DNA-incorporation of 3H-thymidine.
The impact of LPS on proteins related to cell cycle control, as cyclins, cyclin-dependent kinases (CDKs), and CDK-inhibitors was tested. LPS stimulated the protein expression of cyclin D1 and D3, CDK6 and CDK4. Paradoxically, the expression of the CDK-inhibitors p27 and p15 is also increased. Because it is known that the cyclin D1 promoter contains a consensus site for NF-kB, a well identified mediator of LPS action, a role of LPS on cyclin D1 gene expression should be explored.
In conclusion, we evidenced that thyroid cells are able to respond to the proliferative stimulus of LPS, a fact that supports a role of the endotoxin as a potential modifier of thyroid cell replication.
