Lipopolysaccharide stimulates cell proliferation and modifies cell cycle-related proteins in the FRTL-5 thyroid cell line

NAZAR M; NICOLA JP; VELEZ ML; PELLIZAS CG; MASINI-REPISO AM

Gramado, Brasil

Congreso; XIII Latin American Thyroid Congress; 2009

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 is capable of inducing 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 thyroid follicular cells, and that LPS produced a direct action on these, inducing up-regulation of thyroglobulin and Na+/I- symporter gene expression. This study aimed to analyze the effect of LPS on thyroid cell growth in the rat thyroid cell line, FRTL-5. We reveal that LPS increased the proliferation rate of FRTL-5 cells measured by dilution of the intracelullar dye carboxyfluorescein diacetate succinimidyl ester (CFSE), and DNA-incorporation of 3H-thymidine. The impact of LPS treatment on proteins related to cell cycle control, as cyclins, cyclin-dependent kinases (CDK), and CDK-inhibitors was tested. LPS stimulated the protein expression of cyclin D1 and D3. CDK6 and CDK4 were up-regulated by the treatment. Paradoxically, CDK-inhibitors p27 and p15 also increases. Because it’s known that cyclin D1 promoter has a site for NF-kB, a well identified effector of LPS actions, this pathway justify be study. Increasing experimental evidence indicates that chronical inflammatory processes that may lead to tumorigenesis are mediated in part through recognition of a range of stimulus by TLR4. The fact that thyroid cells are able to recognize and respond to LPS supports a role of the endotoxin as a potential modifier of thyroid function.