Interaction between thyroid hormones and the immune system is reported in the literature. Thyroid hormones, thyroxine, T-4, but also T-3, act non-genomically through mechanisms that involve a plasma membrane receptor alpha v beta 3 integrin, a co-receptor for insulin-like growth factor-1 (IGF-1). Previous data from our laboratory show a crosstalk between thyroid hormones and IGF-1 because thyroid hormones inhibit the IGF-1-stimulated glucose uptake and cell proliferation in L-6 myoblasts, and the effects are mediated by integrin alpha v beta 3. IGF-1 also behaves as a chemokine, being an important factor for tissue regeneration after damage. In the present study, using THP-1 human leukemic monocytes, expressing alpha v beta 3 integrin in their cell membrane, we focused on the crosstalk between thyroid hormones and either IGF-1 or monocyte chemoattractant protein-1 (MCP-1), studying cell migration and proliferation stimulated by the two chemokines, and the role of alpha v beta 3 integrin, using inhibitors of alpha v beta 3 integrin and downstream pathways. Our results show that IGF-1 is a potent chemoattractant in THP-1 monocytes, stimulating cell migration, and thyroid hormone inhibits the effect through alpha v beta 3 integrin. Thyroid hormone also inhibits IGF-1-stimulated cell proliferation through alpha v beta 3 integrin, an example of a crosstalk between genomic and non-genomic effects. We also studied the effects of thyroid hormone on cell migration and proliferation induced by MCP-1, together with the pathways involved, by a pharmacological approach and docking simulation. Our findings show a different downstream signaling for IGF-1 and MCP-1 in THP-1 monocytes mediated by the plasma membrane receptor of thyroid hormones, integrin alpha v beta 3.

Candelotti, E., De Luca, R., Megna, R., Maiolo, M., De Vito, P., Gionfra, F., et al. (2021). Inhibition by Thyroid Hormones of Cell Migration Activated by IGF-1 and MCP-1 in THP-1 Monocytes: Focus on Signal Transduction Events Proximal to Integrin αvβ3. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 9, 651492 [10.3389/fcell.2021.651492].

Inhibition by Thyroid Hormones of Cell Migration Activated by IGF-1 and MCP-1 in THP-1 Monocytes: Focus on Signal Transduction Events Proximal to Integrin αvβ3

Candelotti, Elena;Maiolo, Mariangela;Gionfra, Fabio;Percario, Zulema Antonia;Polticelli, Fabio;Persichini, Tiziana;Colasanti, Marco;Affabris, Elisabetta
;
Incerpi, Sandra
2021-01-01

Abstract

Interaction between thyroid hormones and the immune system is reported in the literature. Thyroid hormones, thyroxine, T-4, but also T-3, act non-genomically through mechanisms that involve a plasma membrane receptor alpha v beta 3 integrin, a co-receptor for insulin-like growth factor-1 (IGF-1). Previous data from our laboratory show a crosstalk between thyroid hormones and IGF-1 because thyroid hormones inhibit the IGF-1-stimulated glucose uptake and cell proliferation in L-6 myoblasts, and the effects are mediated by integrin alpha v beta 3. IGF-1 also behaves as a chemokine, being an important factor for tissue regeneration after damage. In the present study, using THP-1 human leukemic monocytes, expressing alpha v beta 3 integrin in their cell membrane, we focused on the crosstalk between thyroid hormones and either IGF-1 or monocyte chemoattractant protein-1 (MCP-1), studying cell migration and proliferation stimulated by the two chemokines, and the role of alpha v beta 3 integrin, using inhibitors of alpha v beta 3 integrin and downstream pathways. Our results show that IGF-1 is a potent chemoattractant in THP-1 monocytes, stimulating cell migration, and thyroid hormone inhibits the effect through alpha v beta 3 integrin. Thyroid hormone also inhibits IGF-1-stimulated cell proliferation through alpha v beta 3 integrin, an example of a crosstalk between genomic and non-genomic effects. We also studied the effects of thyroid hormone on cell migration and proliferation induced by MCP-1, together with the pathways involved, by a pharmacological approach and docking simulation. Our findings show a different downstream signaling for IGF-1 and MCP-1 in THP-1 monocytes mediated by the plasma membrane receptor of thyroid hormones, integrin alpha v beta 3.
Candelotti, E., De Luca, R., Megna, R., Maiolo, M., De Vito, P., Gionfra, F., et al. (2021). Inhibition by Thyroid Hormones of Cell Migration Activated by IGF-1 and MCP-1 in THP-1 Monocytes: Focus on Signal Transduction Events Proximal to Integrin αvβ3. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 9, 651492 [10.3389/fcell.2021.651492].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11590/387354
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