Functional Toll-Like Receptor 4 Conferring Lipopolysaccharide Responsiveness Is Expressed in Thyroid Cells
| Autor: | Juan Pablo Nicola, Laura Fozzatti, Ana María Masini-Repiso, Ariel Maximiliano Lucero, Claudia Gabriela Pellizas, María Laura Vélez |
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| Rok vydání: | 2009 |
| Předmět: |
Lipopolysaccharides
Sodium-iodide symporter endocrine system medicine.medical_specialty Transcription Genetic endocrine system diseases CD14 Thyroid Gland Biology Transfection Cell Line Lipid A Mice Endocrinology Internal medicine medicine Animals Toll-like receptor Thyroid hormone receptor Reverse Transcriptase Polymerase Chain Reaction Cell Membrane Thyroid Iodides Flow Cytometry Rats Toll-Like Receptor 4 medicine.anatomical_structure TLR4 RNA lipids (amino acids peptides and proteins) Thyroid function |
| Zdroj: | Endocrinology. 150:500-508 |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | Lipopolysaccharide (LPS), a glycolipid found in the cell wall of Gram-negative bacteria, exerts pleiotropic biological effects in different cell types. LPS is mainly recognized by the Toll-like receptor (TLR) 4/MD2/Cluster of differentiation 14 complex (CD14). We previously demonstrated that LPS produced a direct action on thyroid cells, including up-regulation of thyroglobulin gene expression. This work aimed to study further the effect of LPS on thyroid function and to elucidate the mechanism by which LPS is recognized by the thyroid cell. We could detect the transcript and protein expression of TLR4, MD2, and CD14 in thyroid cells, and that these proteins are localized at the plasma membrane. The sodium iodide symporter (NIS) is the transporter involved in the iodide uptake, the first step in thyroid hormonogenesis. We demonstrated that LPS increases the TSH-induced iodide uptake and NIS protein expression. The LPS agonist lipid A reproduced LPS effect, whereas the LPS antagonist, polymyxin B, abrogated it. By the use of anti-TLR4 blocking antibodies and the transient expression of TLR4 dominant-negative forms, we evidenced the involvement of TLR4 in the LPS action. The enrichment of TLR4 expressing Fisher rat thyroid cell line-5 (FRTL-5) cells confirmed that TLR4 confers LPS responsiveness to thyroid cells. In conclusion, we revealed for the first time that all the components of the LPS receptor complex are expressed in thyroid cells. Evidence that the effects of LPS on rodent thyroid function involve TLR4-induced signaling was obtained. 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. |
| Databáze: | OpenAIRE |
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