PMID- 33898447 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210428 IS - 2296-634X (Print) IS - 2296-634X (Electronic) IS - 2296-634X (Linking) VI - 9 DP - 2021 TI - 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 alphavbeta3. PG - 651492 LID - 10.3389/fcell.2021.651492 [doi] LID - 651492 AB - 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 alphavbeta3 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 alphavbeta3. 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 alphavbeta3 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 alphavbeta3 integrin, using inhibitors of alphavbeta3 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 alphavbeta3 integrin. Thyroid hormone also inhibits IGF-1-stimulated cell proliferation through alphavbeta3 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 alphavbeta3. CI - Copyright (c) 2021 Candelotti, De Luca, Megna, Maiolo, De Vito, Gionfra, Percario, Borgatti, Gambari, Davis, Lin, Polticelli, Persichini, Colasanti, Affabris, Pedersen and Incerpi. FAU - Candelotti, Elena AU - Candelotti E AD - Department of Science, Roma Tre University, Rome, Italy. FAU - De Luca, Roberto AU - De Luca R AD - Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States. FAU - Megna, Roberto AU - Megna R AD - Department of Science, Roma Tre University, Rome, Italy. FAU - Maiolo, Mariangela AU - Maiolo M AD - Department of Science, Roma Tre University, Rome, Italy. FAU - De Vito, Paolo AU - De Vito P AD - Department of Biology, Tor Vergata University, Rome, Italy. FAU - Gionfra, Fabio AU - Gionfra F AD - Department of Science, Roma Tre University, Rome, Italy. FAU - Percario, Zulema Antonia AU - Percario ZA AD - Department of Science, Roma Tre University, Rome, Italy. FAU - Borgatti, Monica AU - Borgatti M AD - Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy. FAU - Gambari, Roberto AU - Gambari R AD - Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy. FAU - Davis, Paul J AU - Davis PJ AD - Department of Medicine, Albany Medical College, Albany, NY, United States. AD - Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, United States. FAU - Lin, Hung-Yun AU - Lin HY AD - Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, United States. AD - Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan. AD - Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. AD - Traditional Herbal Medicine Research Center of Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan. AD - TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Polticelli, Fabio AU - Polticelli F AD - Department of Science, Roma Tre University, Rome, Italy. FAU - Persichini, Tiziana AU - Persichini T AD - Department of Science, Roma Tre University, Rome, Italy. FAU - Colasanti, Marco AU - Colasanti M AD - Department of Science, Roma Tre University, Rome, Italy. FAU - Affabris, Elisabetta AU - Affabris E AD - Department of Science, Roma Tre University, Rome, Italy. FAU - Pedersen, Jens Z AU - Pedersen JZ AD - Department of Biology, Tor Vergata University, Rome, Italy. FAU - Incerpi, Sandra AU - Incerpi S AD - Department of Science, Roma Tre University, Rome, Italy. LA - eng PT - Journal Article DEP - 20210408 PL - Switzerland TA - Front Cell Dev Biol JT - Frontiers in cell and developmental biology JID - 101630250 PMC - PMC8060509 OTO - NOTNLM OT - PI3-kinase and ERK1/2 signaling pathways OT - STAT-1 OT - baicalein OT - cytokine OT - molecular docking OT - nitric oxide OT - reactive oxygen species OT - tetrac COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with one of the authors RDL. EDAT- 2021/04/27 06:00 MHDA- 2021/04/27 06:01 PMCR- 2021/01/01 CRDT- 2021/04/26 05:57 PHST- 2021/01/10 00:00 [received] PHST- 2021/03/04 00:00 [accepted] PHST- 2021/04/26 05:57 [entrez] PHST- 2021/04/27 06:00 [pubmed] PHST- 2021/04/27 06:01 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fcell.2021.651492 [doi] PST - epublish SO - Front Cell Dev Biol. 2021 Apr 8;9:651492. doi: 10.3389/fcell.2021.651492. eCollection 2021.