TY - JOUR
T1 - Inhibition by Thyroid Hormones of Cell Migration Activated by IGF-1 and MCP-1 in THP-1 Monocytes
T2 - Focus on Signal Transduction Events Proximal to Integrin αvβ3
AU - Candelotti, Elena
AU - De Luca, Roberto
AU - Megna, Roberto
AU - Maiolo, Mariangela
AU - De Vito, Paolo
AU - Gionfra, Fabio
AU - Percario, Zulema Antonia
AU - Borgatti, Monica
AU - Gambari, Roberto
AU - Davis, Paul J.
AU - Lin, Hung Yun
AU - Polticelli, Fabio
AU - Persichini, Tiziana
AU - Colasanti, Marco
AU - Affabris, Elisabetta
AU - Pedersen, Jens Z.
AU - Incerpi, Sandra
N1 - Funding Information:
Funding. A financial support, CAL, from the Department of Sciences, Roma Tre University to SI is gratefully acknowledged.
Funding Information:
A financial support, CAL, from the Department of Roma Tre University to SI is gratefully acknowledged.
Publisher Copyright:
© Copyright © 2021 Candelotti, De Luca, Megna, Maiolo, De Vito, Gionfra, Percario, Borgatti, Gambari, Davis, Lin, Polticelli, Persichini, Colasanti, Affabris, Pedersen and Incerpi.
PY - 2021/4/8
Y1 - 2021/4/8
N2 - Interaction between thyroid hormones and the immune system is reported in the literature. Thyroid hormones, thyroxine, T4, but also T3, act non-genomically through mechanisms that involve a plasma membrane receptor αvβ3 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 αvβ3. 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 αvβ3 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 αvβ3 integrin, using inhibitors of αvβ3 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 αvβ3 integrin. Thyroid hormone also inhibits IGF-1-stimulated cell proliferation through αvβ3 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 αvβ3.
AB - Interaction between thyroid hormones and the immune system is reported in the literature. Thyroid hormones, thyroxine, T4, but also T3, act non-genomically through mechanisms that involve a plasma membrane receptor αvβ3 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 αvβ3. 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 αvβ3 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 αvβ3 integrin, using inhibitors of αvβ3 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 αvβ3 integrin. Thyroid hormone also inhibits IGF-1-stimulated cell proliferation through αvβ3 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 αvβ3.
KW - baicalein
KW - cytokine
KW - molecular docking
KW - nitric oxide
KW - PI3-kinase and ERK1/2 signaling pathways
KW - reactive oxygen species
KW - STAT-1
KW - tetrac
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UR - http://www.scopus.com/inward/citedby.url?scp=85104660558&partnerID=8YFLogxK
U2 - 10.3389/fcell.2021.651492
DO - 10.3389/fcell.2021.651492
M3 - Article
AN - SCOPUS:85104660558
SN - 2296-634X
VL - 9
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
M1 - 651492
ER -